Saturday, March 29, 2014

Ooh Child...uplifting sweetness from Nina Simone, The Five Stairsteps, and Steven!!!

Pick your preferred potion below, but I guarantee a gentle smile either way.  Yes, the road of life always has bumps, ridges, potholes, and even sinkholes!  Cars run off the rails, dreams shatter, pain shows up, and some days are lonelier than can be imagined.  There is an expiration date for all of us.  But, it's not today.  SO.....I'm going to use TODAY as best as I possibly can.  And since dear, sweet Steven was kind enough to send this bit of joy my way, I want to pay it forward and share it with you.

Ooh-oo child, Things are gonna get easier.  Ooh-oo child, Things'll get brighter. 
Some day, yeah.  We'll get it together and we'll get it all done.
Some day, when your head is much lighter.
Some day, yeah.  We'll walk in the rays of a beautiful sun.
Some day, when the world is much brighter.
Ooh-oo child, Things are gonna get easier.  Ooh-oo child, Things'll get brighter.

 Ooh Child - The Five Stairsteps

Ooh Child - Nina Simone

Wishing a brighter day for each of you.  Thanks, Steven. - c

Thursday, March 27, 2014

Anti-PDL1 for melanoma: A Phase 1 trial of MEDI4736 in Combination With Dabrafenib and Trametinib or With Trametinib Alone

A Phase 1 Open-label Study of Safety and Tolerability of MEDI4736 in Combination With Dabrafenib and Trametinib or With Trametinib Alone 

The study above is now recruiting.  You can see all the details on by entering the NCT#.  Some folks on the forums are asking questions about it so I thought I could  try to answer a few points here.

Dabrafenib (Tafinlar) is a BRAF inhibitor that achieves a 70-80% response rate in melanoma patients with the BRAF v600E mutation.  Its down sides include the fact that the response can come with some nasty side effects and it can cease working for many melanoma patients in 6-9 months, though there are some out there who have done great for years. (You know you're the man Dick K!!!)  Trametinib (Mekinist) is a downstream inhibitor in the same pathway as the BRAF inhibitors.  The good news is that it seems to work in patients with NRAS mutations as well as those having the BRAF v600E mutation.  Recently the combo of these drugs was approved and is helping patients get rid of their tumors with fewer side effects and with less chance of melanoma learning how to work around the drugs.  (I have posts on Jan 13, 2013 and more recently on Feb 13, 2014 with more information on these drugs.)

MEDI4736 is an anti-PDL1 drug produced by MedImmune.  Anti-PDL1 is an antibody that blocks a switch on a melanoma cell that turns off your immune system.  Anti-PD1 drugs, are antibodies that block the switch on the white cells so that they can attack melanoma.

As someone who (along with most of the folks in my BMS anti-PD1 (Nivo) study at Moffitt) has had my tumor tested for the expression of PD-L1 on its surface...I have a very specific interest in the intel coming out about the anti-PDL1 drugs.   Back in 2012, The New England Journal of Medicine noted that in patients from a Nivo study, with a variety of tumor types, 25 of the 42 patients tested had tumors that were positive for PD-L1.  "Of these 25 patients, 9 had an objective response.  NONE of the 17 patients with PD-L1 NEGATIVE tumors had an objective response."  NOW...with that said....since then I have been told by the folks at Moffitt that that data was really important AND also told that it didn't mean so much after all.  We have still NOT been told what our personal tumors tested out to be...nor have I seen a report on that data.
To back up a step here is a basic info report on a different anti-PDL1 product:  Promising drug prevents cancer cells from shutting down immune system  
31 May 2013 19:19:03
"An investigational drug that targets the immune system’s ability to fight cancer is showing promising results in Yale Cancer Center (YCC) patients with a variety of advanced or metastatic forms of the disease. Updated data from this Phase 1 clinical trial are being formally presented at the 2013 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Yale Cancer Center is one of the lead trial sites. The abstract was made public by ASCO in advance of the meeting.
The drug, known as MPDL3280A and manufactured by Roche Genentech, is designed to prevent a cancer cell’s mutated and overexpressed PD-L1 gene protein from putting the immune system to sleep. The overexpressed PD-L1 protein turns off the immune system’s T-cells by binding to its PD-1 and B7.1 proteins. In doing so, it disguises itself and evades detection and destruction by the body’s immune response.
This new drug is the latest advance in the burgeoning field of immunotherapy, which aims to boost the body’s immune system to fight the foreign pathogens of cancer. By blocking the cancer tumor’s PD-L1 protein, MPDL3280A frees the immune system to do its job. This PD-L1 targeted antibody was specially engineered to increase safety and efficacy over earlier immunotherapy agents.
Yale oncologists report that the efficacy of MPDL3280A was evaluated in 140 patients with locally advanced or metastatic solid tumors who had exhausted other means of therapy. Tumor shrinkage was observed in patients with non-small cell lung cancer, melanoma, kidney cancer, colorectal cancer, and gastric cancer. Yale oncologists say ongoing, durable responses were observed in nearly all patients who responded to the drug. Overall, 29 out of 140 patients (21 percent) experienced significant tumor shrinkage, and the highest number of responses were in patients with lung cancer and melanoma.
MPDL3280A was generally well tolerated, they say, with few immune-related adverse events. Some patients were continuing to respond more than a year after starting treatment.
“We have been very impressed by the response in seriously ill patients whose cancer had metastasized. So far, almost none of those who showed tumor shrinkage have gotten worse, which is extraordinary,” said lead author Roy Herbst, M.D., professor of medicine and chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital at Yale-New Haven. “Immunotherapy treatment is providing new hope for cancer patients,” he added."
Currently there is a Phase 2 study ongoing, using anti-PDL1 with avastin in renal cell carcinoma.  There is also a Phase 3 study in progess using anti-PDL1 in patients with non-small cell lung cancer.  Neither of these studies have published outcomes thus my knowledge.
From ASCO, 2013:  A study of MPDL3280A (engineered anti-PDL1):  Activity, safety, and characterization of immune response in pre- and on-treatment tumors in metastatic melanoma patients.  Sosman, Hamid, Lawrense, Flaherty, Hodi, et al.
"Melanoma tumor cells may utilize PD-L1 overexpression to escape immune surveillance...In Phase 1 study, metastatic melanoma patients received MPDL3280A IV every 3 weeks for up to 1 year and had tumor assessments every 6 weeks.  As of Feb 2013, 44...patients dosed at 0.1-20mg/kg were evaluated...61% received >/= 1 prior systemic regimen and 36% received prior immunotherapy.  14% of patients experienced grade 3/4 treatment related adverse events, including [elevated liver enzymes].  No grade 3-5 pneumonitis or colitis was reported. 38...patients...dosed at 1-20mg/kg prior to August 2012 were evaluable...An objective response rate of 32% (11/34) was observed in patients with cutaneous, mucosal or unknown primary histology (0/4 ocular patients responded).  Resection of remaining mass in a responding patient after 1 year of therapy showed no evidence of viable tumor.  Responses were durable, with 10/11 ongoing (responding patients on study for 3-10.5 months).  Analysis of archival tumor samples showed that PD-L1 positive patients had a higher rate of disease control versus PD-L1 negative patients [87% vs 20%]."
Clearly, as there is no data out on the combo this clinical trial is examining (to my knowledge) I don't have any intel to add that addresses that specifically.  But, for those of you with interest in the trial and its components....perhaps this background information will be helpful.
Wishing you all my best - c

Sunday, March 23, 2014

One of the sweetest women I have ever known lost her son today.

It was not as though she misplaced him.  He did not suffer from melanoma or other untreatable disease.  No....he died a completely preventable....NO!! EASILY PREVENTABLE...death.  As a society, we could make such loss a thing of the past. A relic of bygone days when men knew no better.  He died because an asshole took a gun to a bar.  Yep.  Good idea don't you think?  So, Mr. LaPierre and all you other great, old, white hunters of're going to have to explain this to me one more time.  Exactly WHOSE rights did we preserve and protect today???  Would it make any difference to you if he had been YOUR son?  Cause I've got news for you.  He was.

Thursday, March 20, 2014

Should Melanoma Brain Met patients be allowed in clinical trials???

It still hurts my heart (and my head) that so many people fail to see reason and understand why many of the new treatments for melanoma can't be viewed like old time chemo when it comes to deciding whether to allow melanoma brain met patients to have them!!!  When thinking about the use of novel therapies (ipi and anti-PD1) in regard to brain metastasis, studies and the method of action of these drugs make it clear that the action upon brain mets is NOT due to the DRUG "crossing the blood brain barrier," but for the activated cytotoxic T-cells to do so. In my own study of resected metastatic melanoma patients with Nivo, all 6 of us who had metastatic brain mets out of the 30 in our arm, begun in 2010, were still alive and kicking with NO RELAPSE as of September 2013. Weber and many other researchers have contended for some time that drugs like Ipi and anti-PD1 have as good an effect in the brain as they do in the body. Additionally, in a nivo treatment arm at Moffitt that allowed brain met patients, 1 of the patient's brain mets resolved on nivo ALONE...with NO OTHER TREATMENT. To say they are excited is a definite understatement!

In his presentation and interview @ ASCO, June 2013 - Melanoma: Long overall survival in patients receiving Nivolumab, ...When asked about the likelihood that the drug works on brain metastases, Sznol noted that this trial excluded patients with active brain lesions, but accepted patients with previously-treated central nervous system tumors. Therefore the answer to the question remains unknown. "But we have long-term responders who didn't develop any brain metastases, so that suggests that maybe we are controlling disease in the brain," he said.

Phase II trial of ipi monotherapy in melanoma patients with brain metastases, by Lawrence et al.
CONCLUSION: Ipi has a similar level of activity in brain and non-CNS lesions.

Novel treatments for Melanoma brain Metastases, by Kenchapp et al. 2013. Looked at a study using ipi..."this study revealed that ipi has activity in melanoma brain is unknown whether the treatment was more effective in larger melanoma brain mets in which the highly permeable blood brain barrier may allow greater ingress of activated cytotoxic T cells."

And finally, Melanoma Brain Metastases: Is it time to reassess the bias? By: Flanigan, Sznol, et al. July 2012. These authors note that melanoma brain met patients are typically excluded from trials. They conducted a chart review of 251 metastatic melanoma patients diagnosed after 2005 to evaluate them in the context of eligibility for treatment with novel agents. And "found median survival of malignant effusion (mets in the pleural cavity) patients was significantly shorter than brain met patients (2 vs 8 months)." Therefore, "exclusion of melanoma brain met patients from clinical research programs is no longer justified and alternate investigational approaches, possibly combining local and systemic therapies, are greatly needed for these individuals."

So....lots of folks ARE on our side!!! Hopefully, archaic, irrational decisions will give way to what the data shows very soon and more patients with metastatic melanoma mets to the brain will have greater treatment options, as the data shows more and more the reality of our situation. - c

Tuesday, March 18, 2014

Melanoma patients teach us more about complications with Ipi

As more melanoma patients utilize Ipilimumab (Yervoy) for treatment, we are all learning more about potential side effects as well as ways to deal with them.

Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution.  Ryder, Wolchok, et al.  Edocr Relat Cancer.  2014 March 7.

"Novel immune checkpoint blockade with [ipi], an antibody blocking the cytotoxic T-lymphocyte antigen 4 is revolutionizing cancer therapy.  However, [ipi] induces symptomatic and sometimes severe, endocrine immune-related adverse events that are inconsistently recognized and reported."  In a retrospective study these folks looked at 256 records of patients receiving ipi in clinical trials between 2007 and 2013.  They looked at their hormone related labs, X-ray results, and clinical histories.  After ipi, they found that the patients demonstrated an 8% incidence of hypophysitis, 6% dealt with hypothyroidism/thyroiditis, and primary adrenal dysfunction was rare.  When Nivo and ipi
were given together, there was a 22% incidence of either thyroiditis or hypothyroidism, and a 9% incidence of hypophysitis.  "Symptomatic relief, in particular, for hypophysitis, was achieved in all patients with hormone replacement, although endogenous hormone secretion was rarely recovered."  "Prompt initiation with hormone replacement reverses symptoms."

Atypical neurological complications of ipilimumab therapy in patients with metastatic melanoma.  Liao, et al. Neuro Oncology. 2014 Jan 30. [Epup ahead of print]

"Ipi is a novel FDA approved recombinant human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 and has been used to treat patients with metastatic melanoma.  Immune-related side effects include inflammatory myopathy, aseptic meningitis, posterior reversible encephalopathy syndrome, Guillain-Barre' syndrome, myasthenia gravis-type syndrome, sensorimotor neuropathy, and inflammatory enteric neuropathy.  To date, there is no report for ipi-induced chronic inflammatory demyelinating polyneuropathy (CIDP), transverse myelitis, or concurrent myositis and myasthenia gravis-type syndrome."  So....these peeps wanted to get the word out about what they saw in their patients and what they did about it.  They had three patients to develop the last three syndromes after treatment with ipi at MD Anderson between July 2012 and June 2013.  Median time to onset of adverse effects after ipi was 1-2 weeks.  Ipi was discontinued.  Plasmapheresis (in which the antibodies in the plasma are skimmed off and the red blood cells returned to the patient) was initiated in the patient with CIDP and the concurrent myositis and myasthenia gravis-type syndromes.  High dose steroids were given to the other patient. The patients got better.  "Conclusion:  Ipi could induce a wide spectrum of neurological adverse effects.  Our findings support the standard treatment of withholding or discontinuing ipi.  Plasmapheresis or high-dose IV steroids may be considered as...initial treatment...  Improvement...may be seen within 2 weeks."

SO....Tricky business!!! Clearly Yervoy [ipi] can provide great help in treating melanoma but it is important to be aware of  potential side effects.  I'm glad they are putting this kind of information out there for doctors and patients since it seems that once such side effects are recognized for what they are...treatments and help are available.  Hang in there. - c

Wednesday, March 12, 2014

Expanded Access Program for Merck's anti-PD1 (MK-3475/Lambrolizumab) from my thoughts and questions

Program for MK-3475 in Participants With Metastatic Melanoma Who Have Failed Standard of Care Therapy Including Ipilimumab (MK-3475-030)

Expanded access is currently available for this treatment.
Verified March 2014 by Merck Sharp & Dohme Corp.
Sponsor:  Merck Sharp & Dohme Corp. Identifier:  NCT02083484
First received: March 7, 2014
Last verified: March 2014 

This is an expanded access program (EAP) for participants who have progressed after prior systemic therapy including ipilimumab, and V-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor or mitogen-activated protein kinase (MEK) enzyme inhibitor when indicated. Participants cannot be eligible for or have participated in any MK-3475 clinical trial.

Biological: MK-3475

Study Type:
Expanded Access     [EXPANDED ACCESS =A process regulated by the Food and Drug Administration (FDA) that allows manufacturers to provide investigational new drugs to patients with serious diseases or conditions who cannot participate in a clinical trial.
For more information on expanded access programs, please visit the FDA Web site at ]
Official Title:
Expanded Access of MK-3475 in Metastatic Melanoma Patients With Limited to No Treatment Options
Intervention Details:
Biological: MK-3475
Each participant will receive MK-3475 every 3 weeks for up to 2 years or until confirmed radiographic disease progression, unacceptable toxicity, confirmed positive pregnancy test, withdrawal of consent, or MK-3475 approval in the participant's country.
Ages Eligible for Study:  
12 Years and older
Genders Eligible for Study:  

Inclusion criteria:
  • Unresectable (Stage III) or metastatic melanoma
  • Failed or progressed on standard of care systemic therapy including ipilimumab
  • Willing to sign Informed Consent
  • Eastern Cooperative Oncology Group Performance status of 0 or 1
  • Female participants of childbearing potential must be willing to use adequate contraception or be surgically sterile, or abstain from heterosexual activity starting with the first dose of treatment through at least 120 days after the last dose of MK-3475
  • Male participants must agree to use an adequate method of contraception starting with the first dose of treatment through 120 days after the last dose of MK-3475
  • Adequate organ function
Exclusion criteria:
  • Eligible for an accessible MK-3475 clinical study or previously participated in a MK-3475 clinical study
  • Eligible for treatment with a marketed BRAF/MEK inhibitor
  • Not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better due to prior chemotherapy, radioactive, or biological cancer therapy (including monoclonal antibodies)
  • Not recovered from minor or major surgery and less than 4 weeks from major surgery
  • History of life-threatening or severe immune-related adverse events on treatment with another immunotherapy
  • Expected to require any other form of systemic antineoplastic therapy while receiving MK-3475
  • History of clinically severe autoimmune disease (e.g., requires chronic immunosuppressive therapy)
  • History of pneumonitis, organ transplant, human immunodeficiency virus (HIV), active hepatitis B or hepatitis C
  • Active central nervous system metastases, carcinomatous meningitis, untreated brain metastases
  • Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of treatment with MK-3475
  • Active infection requiring systemic therapy
Contacts and Locations:  Please refer to this study by its identifier: NCT02083484  Contact:  1-855-478-43471-855-478-4347

1.  This is good news.  Anytime a drug that has a positive effect is available for more folks in need, that is a very good thing indeed.
2. In the pandemonium that has surrounded this announcement it is important to remember what studies show this drug can offer.  In Merck's first Phase 1B study with this anti-PD1 product, once follow-up data was added, overall response rate was 41%, with 88% of patients who demonstrated partial or complete responses, showing no evidence of disease progression.
3.  For what it is worth, Dr. Weber, who is currently running trials with both the BMS and Merck anti-PD1 drugs, feels that they will both pan out with approximately the same overall results.
1.  Exclusions include - "history of life-threatening or severe immune-related adverse event" on prior immunotherapy.   Who decides?  Is an admission for colitis on ipi, though now recovered, considered a "severe immune-related adverse event"?  Is ipi induced hypothyroidism?
2.  I assume that "failed or progressed on standard of care systemic therapy including ipi"  also includes IL2?  other anti-PD1 products? (Various folks on the forums are saying that failing anti-PD1 products other than Merck's allow inclusion, though it is not clearly stated here.)
3.  If BRAF positive, it seems that you must go ahead and use that option, then fail/progress in order to gain access to MK-3475.  Would this be something I wanted to do first, if I had minimal disease burden?  I don't know the answer to that.  But, I think it would be a hard thing for me to decide.
4. Since not explicitly stated, must one have failed on ALL of the above?  If you have one of these "systemic therapies" left untried, must you do, say...IL2, before you can gain access?  Even though you failed ipi and BRAF?
5.  An additional exclusion, is if you are "eligible for an accessible MK-3475 clinical study."  Does this mean that if there were a study with MK-3475 vs say...dacarbazine...and you got the dacarbazine are stuck with that and ineligible for expanded access?  What is accessible?  If there is an expanded access option within 30 minutes of your home, but an MK-3475 trial slot open several hours away....must you take the trial slot?
6.  Who will pay for the drug?  I am not saying there will be a charge, but it doesn't say there will NOT be, either.  The company could petition the FDA for the ability to charge the patient. Additionally, will facilities providing the drug charge the patient? Again, they could petition the FDA as well.  You can check the links below for additional info.

Hopefully the answers to these questions will be clarified very soon and patients with few remaining options will be given another viable solution!!!
Fingers crossed - c

Monday, March 10, 2014

9 months after Nivolumab trial...stats, f/u, what we learned....

Latest stats:
127 months - since melanoma diagnosis (over 10 1/2 years!!!)
47 months - Stage IV (almost 4 years)
41 months - NED
39 months - since start of Nivolumab (anti-PD1 trial)

Scans (the usual CT of neck, chest, and abdomen with an MRI of the brain) on 2/28 were all negative for melanoma lesions.  Bent shipped the reports and CD's off to Tampa as usual and we were on our way for a 6 month recheck, after a 3 month follow-up done in September, with my last infusion of bug juice in June 2013.  We drove to Atlanta with no real excitement on the 6th, for a pretty easy flight down to Tampa...despite their sightings of water spouts!!!....that afternoon.  Here's the story...

Our flight was a bit later than our usual, but that worked out for the best, as Tampa weather had cleared by the time we landed.  B had known the weather probably wouldn't be that great, so rather than any grand adventure, we had decided to pick up supper at  the Pho Quyen location nearest our La Quinta.  Is Tampa a Scrabble lover's town or what??? (You know the one, Ruthie.  In the corner of the shopping area with the grocery store where the lady liked your nail polish and the horrible Jason's Deli??!!)  BUT!  The night before we were to leave, B gets an email from a wine club we joined when we were in Sonoma.  Peter Spann, of Spann wines, was to be doing a Tampa....Thursday evening!!!  He's a vintner (And I mean a hands on one!!!....his hands were stained purple when we met him!) Brent and I met at Bungalow 313 in Sonoma in October of 2011.  We joined his wine club back then.  (I'm telling you, the wines he and his wife makes are amazing.  You should definitely check them out!!)  Brent was so excited.  He and Peter have chatted on the phone over the years, with their last conversation just a couple of weeks ago! We landed at 6:30.  The tasting was to be over at 7.  I didn't care.  This was going to happen!!! We dashed to the rental car place.  No cars in the compact line.  No cars in the economy line.  I'm checking out a Kia, Sol..located in the "standard" line-up.  As ever in Alamo's fluid roster, it HAS been designated in both categories before!  I find it acceptable as B rushes to the kiosk.  With a wave, the attendant says it's ours since there ARE no others.  We're off!!!  The GPS can't manage to get over its attachment to other cities and goes a bit wonky for a while.  B calls the location of the tasting...yes, Peter Spann is there...yes, he'll be there for a while longer.  We get headed in the right direction.  Gotta say, that Sol's got pretty good pick-up.  I fear Peter will tag B as a stalker.  We pull in.  Fair size gathering in a little wine shop.  We are greeted by the owners of the shop and enjoy a sip.  Peter is chatting with another gentleman.  Turns out we had a great time with Peter and a school chum of his who happens to live in the Tampa area.  They were meeting up for the first time in 40 years!!!  In fact, we ended up going to dinner with them at Pho Quyen!!  It was a pleasure to listen to the stories of strangers, who now aren't quite!!!

Our visit to Moffitt began at the butt crack of Tampa dawn...0700!!!  That's how we roll in Tampa town!  For the first time in over three years, our visit started on the first floor in a little lab rather than in the CRU (Clinical Research Unit) and I did not have an IV started or 15 tubes of research labs drawn!!!!  You'd think that would be easy right?  Well, cute little girl had a panic attack about my new insurance, that Brent had already checked with Moffitt about, but was finally cleared to her satisfaction after she called more important billing people.  The next cute little girl managed to blow my vein after digging around in it for a bit, while asking...."Does that feel normal?"  "Why, yes.  Of course it does.  You just poked me with a sharp object, squitched it around for a while, and made a big bruise.  Normal as can be!!!"  Oh, dear...there are worse things....

Off to the "Cutaneous Clinic" i.e. Dr. Weber's office.  He noted that my vitiligo seemed a bit increased, and reported that areas of vitiligo were often preceded by significant itching due to the inflammatory reaction.  (Hmmm...wonder where he first heard that????)  He found the report of my Jan/Feb arthralgias and mouth ulcers interesting and felt they were most certainly immunologic effects, something he reported seeing persist intermittently in some of his younger patients. That was about it for me, but this is what we learned...

In my Stage IV/III melanoma, NED arm of the study:
  • 33 patients have been treated
  • 9 relapsed
  • 4 are deceased
  • 3 are back in remission (I don't know what treatment they were given.)
  • 2 are in treatment currently
Per our discussion, Dr. Weber is feeling very positive about the value of treating folks who are NED with Nivo.  He noted that based on historic data - at this point in our trajectory (about 2 years give or take) he would expect 16 deaths, rather than the 4 that have occurred.  

That is an 87% overall survival rate at 2 years.  The data from this portion of the trial are to be published soon.  Despite continuing to petition BMS for expanded trials utilizing Nivo as an adjunctive and seeking approval for its use in that manner, he has not succeeded thus far.

In the Stage IV metastatic melanoma, NON-resected arm:
  • In a previous study with Nivo, 107 patients were treated every 2 weeks for 2 years with a median survival of 16.8 months.
  • In THIS arm of the Moffitt study, 105 patients have been treated in the manner I was, getting Nivo every 2 weeks for 6 months, then every 3 months for 2 additional years.  The median survival has been 16.7 months.  
  • So...survival was equivalent with less med, fewer trips to the doc, and with sicker patients (ocular mel and a few others were allowed that were not in the first study) in the Moffitt trial.
  • Thus far, the Kaplan-Meier curve at 2 years is hanging at about 20%, but folks at Moffitt feel it will settle out around 25%.
Additional Cohort 6 added:
  • How this cohort is defined specifically, how many have been enrolled in total, how many may still be enrolled, I do not know, however:
  • 5 patients in this cohort were admitted with brain mets.
  • 4 were treated (I presume by radiation...though not certain)
  • BUT...1 experienced a COMPLETE RESPONSE with just Nivo!!!!!  (Awesome, right???!!)
  • There may continue to be open slots here...but I am not at all sure about that.
Additional Arm added:  
  • Due to the needs of, and in cooperation with, a German company...the connection and reasons remained unclear to me....the NED arm, examining the response to Nivo AND ipi, that I noted in my prior post has been added as well.
  • We were told that the news was already out about it before its start, so it has filled very quickly.  However, as of this past Friday...9 slots did remain.
Final thoughts:
  • Dr. Weber feels that his work shows that Nivo is probably NOT needed at a dosing rate of every 2 weeks for 2 years, since he attained the same results as the prior study with fewer doses and sicker patients.
  • While it remains unproven as yet, he also mentioned that "patients who responded, probably had all their melanoma cells eradicated" and "were basically CURED with no need for further treatment after the first course."
  • Yes....he used the "C" word....and I don't mean cancer! 
 It is odd, and somewhat appalling, how very iron clad, yet extraordinarily flexible trial protocols can be. Yes, on this visit, I signed yet another 23 page consent form...noted to be "Version 13" for the same trial I have been in for over 3 years.  No matter how many times you search or utilize any of the search engines I reported on earlier this will NOT get the complete picture of what the trial is offering, its inclusions, nor exclusions.  They change a great deal over time.  If you are interested in ANY trial....or in ANY trial location/facility...CALL the clinical trial coordinator!  The worst you will get  But, you might get a slot in a trial you knew about, or find out about a whole new option that might prove to be the thing you or your loved one really needs!  CALL!
Wishing my very best to you all...especially my rattie peeps! - c

Saturday, March 8, 2014

Openings for Nivolumab Trial in Tampa!!!!

Yes, Virginia...despite the nay-sayers....there really ARE STILL some openings for a Nivolumab trial in Tampa.  Was there Friday and heard it from the horse's mouth and had to sign the amended protocol myself!!!!

Here's the deal:  An additional arm has been added to my clinical trial...technically named:  A phase 1 trial of a vaccine combining multiple class 1 peptides and montanide ISA 51 VG with escalating doses of anti-PD1 antibody BMS-936558 (now known as Nivolumab) for patients with resected stages IIIC/IV melanoma, NCI protocol P-8316.

The new arm = Nivolumab and Ipilimumab Administration
"You will receive your first dose of nivolumab with ipi within 28 days after your screening blood draws.  The dosage of nivo will be 1mg/kg with ipi at 3mg/kg for all patients in this group. Both drugs will be given.  Nivo with ipi will be given as an IV infusion as an outpatient... The next doses of nivo with ipi will be given 3, 6, and 9 weeks after the first. If at week 12 you have not had a return of your tumor, you may also receive additional doses of nivo, this time at 3mg/kg every 2 weeks for up to 2 years....."

For this study you must be NED.  You may have treated brain mets as long as they have been stable for a prescribed length of time.  I am not sure whether any specific HLA typing is required as the patients will NOT be getting the peptide vaccines.  Of course all the details of exclusions, etc. will have to be discussed with Dr. Weber and the trial coordinator. of Friday AM...NINE SLOTS REMAINED AVAILABLE!!!!!!

This trial arm differs from mine in that:
  • I got only nivo at 1mg/kg [another group got 3mg/kg, and another was given 10mg/kg] every 2 weeks for 6 months, then every 3 months for 2 additional years.
  • I got peptide vaccines with the nivo every 2 weeks for 6 months.
Additional Points:
  • FYI - you needn't feel bad about NOT getting the vaccines...the data has already been examined from my peeps and the vaccines did no good.
  • CT scans of neck, chest and abdomen with an MRI of the head were required every three months in my group...and I suspect it will be the same in this one.
  • Dr. Weber had high praise for how well the resected patients in this trial are doing. 
  • He and others are becoming more and more convinced that the lower the disease burden the greater effect immunologic treatments can attain.
It also seemed as though there remain openings in the NON-RESECTED ARM for Nivo as well (though I am not certain)!!!!

But....don't take my word for it.  CALL!!!  The folks running this trial are very accessible. Wishing you all my best.  More on the particulars of my visit coming!!! - c

H. Lee Moffitt Cancer Center & Research Institute
12902 Magnolia Drive
Tampa, FL 33612

Phone: 1-888-MOFFITT (1-888-663-3488)
Moffitt Cancer Center Switchboard:
813-745-4673 or 800-456-3434
Moffitt Cancer Center at International Plaza:

    Thursday, March 6, 2014

    Sweet dreams....

         Whenever there are worries....about my scans, other people's scans, my children, other people's children (the 19 monther who neither walks nor talks, but smiles ever so sweetly, and getting needed evaluations and testing has been a ridiculous insurance/facility nightmare), the "simple" home repairs that turned out to be neither simple nor within budget, one dog that has seizures while the other trees 2 am!!!!.....and one is so tired that sleep won't come....I nudge the softly snoring Bentie.
         "Bent, tell me a story."  A request that is not unexpected in Bentie World.
         "What?  Oh.  Hmmm...... Well, you were in a boat.  And you paddled and paddled until you were far out into the sea.  Then, you came back to me."
         He hugs me gently.  All is right.  And, yes.  I would.  Come back.  No matter how far I paddled. Sweet dreams. - c

    Tuesday, March 4, 2014

    My favorite day ~ March Forth...with a special pic/vid for J& F!!!!

    My sweet love, said, "Come on!  You have to come outside for a minute!!  Come on!"  And there it was, the first crocus of Spring.  Yes, Spring...shall come!!!  Again!  So, March Forth!  With spirit and determination and beauty and love.  All for you today, J!  All for you!!!!

    Scroll down just a bit on the link below.  Forget all the shadow business.  You and F are the peeps who show me the way, teach me who I want to be.....and no! have never gone unnoticed...not by me!  Did you ever know that you are my hero?  I could fly higher than eagle because the two of you are the wind beneath my wings.

    Wind Beneath My Wings

    Thanks for being J & F!  Forever. - c

    Sunday, March 2, 2014

    Searching for Melanoma Trials???! The down low on search engines ~ links included!!!

        Like the inner Cairn Terrier I am, when looking for trial options for some of my melanoma peeps, I got very excited when Brent stumbled upon MDLinx, a pretty user friendly, clinical trial search engine, PLUS found some remaining spots for Nivolumab (BMS' anti-PD1 product)!!!!  And that got me thinking.....      Searching for a clinical trial for yourself or your loved one is pure hell.  I have to say...Brent did all that for me.  He now admits that he spent "tedious, stressful, months searching".  And he's trained to look at this mess!!  We decided to take it on and really look at the search options out there.  Here's what we found......

    General info:  Every clinical trial finder (search engine) we explored uses as their data base.  They vary based on the filter they use and whether you can access a live person to help you with the process. 

    Dr. Google
         Definitely accessible by anyone with a computer, and that's the beauty and the problem.  You can find anything, but you also find everything.  Legitimate trials, studies, and data are out there.  But, so are folks talking about amazing cures after they stood in the sand, looking east, while eating a plum, just after a coffee enema!!!  Then, there are the horror stories of a person doing this thing, then enduring severe pain and the growth of three heads.  So, Dr. Google has to be taken with a grain of salt.  Just like all the bloggers you can find there! ;>)  Some give referenced data and wonderful personal experiences that a qualitative researcher would be lucky to access and others are just off the wall. You'll have to use your personal judgement to determine what makes sense to you.  We found Google most helpful as a jumping off point to the information you do want to find.  Perhaps, one of its best uses, is to research people and places.  By that I mean, when you see a trial or read a study that you are interested in...check out the author, the institution that participated, the folks listed in the references. all means...Google them!!! That can lead you to some actually useful information! 
         Certainly the mac daddy of research trial sites.  All clinical trials conducted in the United States (and actually much of the world) must be registered through NIH.  That's where they get those nifty NCT numbers.  The problem with this site is that it is large, cumbersome, and not terribly current.  They may not have the most up-to-date information about specific studies - including locations or whether the trial is currently enrolling or not. You can enter melanoma in a general search.  You can do an advanced search with a few more particulars.  For instance, when I put in "melanoma" today, I got 1,493 studies.  When I clicked the box, "open studies only" 486 came up. The main problem is, for the most part, you have to click on each individual study and read all it's exclusion and requirement data to see if it fits for you.  There is no good filter to get it to narrow it down very much further for your particular profile.  One other point:  You can't be hatin' on search engines for the strange trials of questionable merit/value they turn up.  ALL TRIALS...every last one of NIH standards and go through FIRST!!!!  For instance:  NCT01072344, Long Term Chamomile Therapy for still recruiting at University of Pennsylvania....if you want to go for it!!!!

         Mdlinx, is a network of 33 web sites that provides a variety of services mostly for physicians...from job listings, to research by topics, ads, etc...but it also has a trial search option.  Not clear whether physicians are paid capitation fees for referral or not.  Anyhow....Once you click on the link above, you have a form in which you can select: the state you want to look at (or look at "all"), the mile radius, phase of trial, and trial ratings....looking at as narrow or as broad a selection as you like.  With very little info beyond melanoma I was given a display of 196 actively recruiting trials, with a description, the quota filled, location, and a rating.  Had I filled in more info, it would also give me the distance.  When I clicked on a trial offered....Phase 1 biomarker of anti-PD1in Advanced told me it is a phase 1 trial, to have 160 participants with only 2/5's enrolled, BMS is the sponsor, a trial conclusion date of 2017, inclusions and exclusions, and a complete list of locations. It has a good filter.  There is no personal profile search (meaning no particular search based on your melanoma history and prior treatment).  It does take "key" words.  You could for instance, enter: 'melanoma brain'....or:  'melanoma anti-PD1'.  There is no access to a live navigator.

         Collabrx is a data analytics company that uses cloud based technology to analyze data, studies, and trials for patients, docs, companies, etc.  There is a large medical board with some big dogs on it.  Fisher and Flaherty are noted as the melanoma reps.  The site states "advisor involvement is without financial compensation." It is unclear if docs get a referral fee when they use this service or not.  But...what the heck!  YOU can use  When you click on the link above you are taken to  a page with a melanoma specific filter that allows you to fill in your stage, primary, BRAF or other mutation status, and answer a few other questions about your condition.  When I put in mine, I got 73 trials with a nice overview of information that might be pertinent to me. doesn't mean I qualify for all those studies.  You still have check each for exclusions and such that the filter doesn't cover.  It seems fairly up-to-date.  Its simultaneous pros and cons are its filter.  It narrows down studies well, but doesn't allow you look "beyond".  For instance, ADC trials did not show up and if you don't know your BRAF status it doesn't give you a list of ANY trials.  There is no live person available to assist. 
         EmergingMed is a commercial organization that provides services for nonprofit entities, including a clinical trial finder.  It is used by MRF, Oncolinks (the engine on MIF), and many others.  They do not make their money by capitation fees. They can provide a search based on your profile (your clinical history) or a general search.  There are some limits in terms of the profile.  There is no 'key word' search.  There is access to a live navigator.  The results lead you to the database.  

    National Cancer Institute - clinical trial search
         This is a subdivision of the National Institute of Health.  It links to the database.  It has a reasonable search engine and you can enter "key" words.  It does not use a clinical profile.  There is live help available for contact if desired.

    Coalition of Cancer Cooperative Groups
         This collective is a group of oncology services who formed a foundation to promote clinical trials.  They use the database as well as information from within their participating groups.  For studies being done by the groups in the cooperative, they have rapid access to changes in those clinical trials.  (Meaning, since they are in the know about their own studies....when they close, how many slots are left, changes in the protocol...they update those studies in real time!!)  Their site won an award in 2008 as 'Best in Show' and 'Best Application for Enhancing Patient Access for Information' from the National Consumer Healthcare Group.  They use your clinical profile as a filter.  They are linked to the American Cancer Society for navigation resources.  

    American Association for Cancer Research...clinical trial finder
         This is an organization that supports cancer research, through various programs, including 'Stand Up to Cancer'.  It uses EmergingMed to power its clinical trial search, but has its own clinical trial navigator (a real human) to help you if you like.  

    Melanoma Hope Network....Trial finder
         This is a nonprofit organization dedicated to melanoma patients.  It has a listing of centers of excellence and specialists in melanoma care. (A great place to get names and institutions to GOOGLE!!!)  A good deal of education and resources are provided on the site.  It offers TWO clinical trial search engines.  One is Collabrx (reviewed above).  The second option is a profile specific search.  No navigator is available for either.

         Finding a clinical trial is a complex and often frustrating process.  Basically, all of the search engines are mining the same data.  The differences relate to how up-to-date their information is kept, how well their search engine works, and whether or not you have access to a human to assist you in the process should you wish it. In the end, you still need a trained medical professional familiar with your circumstances to sort through the trials (once found) to see if they are even possibilities for you.  Some drug companies offer trial listings as they relate to their drugs.  If you know the drug and who makes it, this can be helpful. (This is where that Google search may come in handy...cause if you don't know either of those things, there is no way to utilize Pharma's listings.)  Novartis is a bit of an exception.  They actually have an android app.... Clinical Trial Seek - Novartis ... which does a reasonable job accessing the database and therefore gives you ALL available clinical trial options, rather than only those related to their products as most other drug company sites do.  
         In the end, I would suggest using every resource you can!!!!  That is certainly what I do to help others and definitely what I would do for myself should I have the need.  
         I owe a great debt of appreciation to Bentie, who helped me with days of research for this post.  We learned a lot and hope it will be helpful to those of you in need.  Poor, Bent. Stuck with a Cairn Terrier when he thought he was getting an Afghan Hound!  Good luck to you all! - c