Questions about new trial

Hi,

So sorry for Craig and you to have to battle the beast once again. I have no news of this trial but wanted to say this board is a wealth of info and support so keep checking back. The weekend plus an American Holiday has kept the board quiet, but it is sure to get busier as the week progresses.

Best of luck!

Vermont_Donna

stage 3a, currently doing IPI

Hi,

So sorry for Craig and you to have to battle the beast once again. I have no news of this trial but wanted to say this board is a wealth of info and support so keep checking back. The weekend plus an American Holiday has kept the board quiet, but it is sure to get busier as the week progresses.

Best of luck!

Vermont_Donna

stage 3a, currently doing IPI

Hi Lisa,

I don't have any advice for you on the trials, but I can tell you that the G606R mutation is in in the same region of BRAF as the other mutation that is better known: V600E.  As you can see from the numbers, they are only 6 amino acids apart, which means they may both be activating mutations for that protein.  Although the original studies were done in colon cancer patients, it is possible that any mutation that activates BRAF may have a similar effect and since BRAF has been shown to be important in melanoma, it is certainly worth thinking about.  If Craig has BOTH mutations, I would say it is not clear what the effect on the protein would be, but perhaps someone has studied that.  

The paper that I looked at does not go into detail on the G606R mutation, just some discussion towards the end of the paper.  It seems to be free:  http://cancerres.aacrjournals.org/content/65/14/6063.full.pdf+html

Best of luck to Craig for a successful result on the trial.

ellen – dad's daughter

Hi Lisa,

I don't have any advice for you on the trials, but I can tell you that the G606R mutation is in in the same region of BRAF as the other mutation that is better known: V600E.  As you can see from the numbers, they are only 6 amino acids apart, which means they may both be activating mutations for that protein.  Although the original studies were done in colon cancer patients, it is possible that any mutation that activates BRAF may have a similar effect and since BRAF has been shown to be important in melanoma, it is certainly worth thinking about.  If Craig has BOTH mutations, I would say it is not clear what the effect on the protein would be, but perhaps someone has studied that.  

The paper that I looked at does not go into detail on the G606R mutation, just some discussion towards the end of the paper.  It seems to be free:  http://cancerres.aacrjournals.org/content/65/14/6063.full.pdf+html

Best of luck to Craig for a successful result on the trial.

ellen – dad's daughter

I apologize if I am too elementary in my explanation, but I don't know how much you are up to speed on melanoma treatments.

Most treatment for melanoma has focused on trying to get the immune system to work better and identifying and destroying tumor cells.  Interferon, Interleukin-2, TIL cell therapy, and ipilimumab are all immunotherapy approaches.  Most of them don't work very well, but the are better than much else that is out there.  Interferon has a response rate that is minimal.  IL–2 is about 14%, but is only given in very healthy patients.  "ip" is new and is a bit better–around 20%.

Chemotherapy, which is commonly used in other cancers, generally doesn't work well in melanoma.  Chemotherapy drugs essentially poison cells, and the fastest growing cells–cancer cells–take up more of the poison that any other cell.  The idea is to give enough to kill the cancer but not so much that it kills off too many normal cells.  (Hair cells and the cells that line the gut also grow quickly, which is why chemo often results in hair loss and nausea.)  DTIC–the control arm of the study you mention–is the best of the chemo bunch in melanoma, with a response rate of about 20% and a duration of about 5 months.  In other words, one out of five patients who take it have a good response, and that response lasts for a few months before the tumors come back.

A newer approach is to find compounds that go into tumor cells and shut them down.  The trial you mention is based on that concept.  About half of melanoma patients have a mutation in a gene callled B-raf.  The protein that this gene forms, BRAF, is part of a chain reaction that tells cell to grow.  In normal cells, the body sends a signal that hits the cell wall and translates into the cell to start this chain reaction.  When B-raf is mutated, the BRAF protein is continually turned on, even without the signalling that is supposed to start the chain reaction.  So, the cell just keeps growing and dividing without control.

The trial you mention tests a new drug being developed by Glaxo SmithKline that inhibits BRAF.  The idea is that by doing this, they can shut down the cell growth.  Roche has a similar drug that is a bit further along in development and is showing a lot of promise.  It has response rates of over 60% but also does not generally result in a durable response.  This particular trial has two arms–the GSK BRAF inhibitor, and DTIC.  Patients are randomized into one or the other arm.

I hope this helps!

Tim–MRF

I apologize if I am too elementary in my explanation, but I don't know how much you are up to speed on melanoma treatments.

Most treatment for melanoma has focused on trying to get the immune system to work better and identifying and destroying tumor cells.  Interferon, Interleukin-2, TIL cell therapy, and ipilimumab are all immunotherapy approaches.  Most of them don't work very well, but the are better than much else that is out there.  Interferon has a response rate that is minimal.  IL–2 is about 14%, but is only given in very healthy patients.  "ip" is new and is a bit better–around 20%.

Chemotherapy, which is commonly used in other cancers, generally doesn't work well in melanoma.  Chemotherapy drugs essentially poison cells, and the fastest growing cells–cancer cells–take up more of the poison that any other cell.  The idea is to give enough to kill the cancer but not so much that it kills off too many normal cells.  (Hair cells and the cells that line the gut also grow quickly, which is why chemo often results in hair loss and nausea.)  DTIC–the control arm of the study you mention–is the best of the chemo bunch in melanoma, with a response rate of about 20% and a duration of about 5 months.  In other words, one out of five patients who take it have a good response, and that response lasts for a few months before the tumors come back.

A newer approach is to find compounds that go into tumor cells and shut them down.  The trial you mention is based on that concept.  About half of melanoma patients have a mutation in a gene callled B-raf.  The protein that this gene forms, BRAF, is part of a chain reaction that tells cell to grow.  In normal cells, the body sends a signal that hits the cell wall and translates into the cell to start this chain reaction.  When B-raf is mutated, the BRAF protein is continually turned on, even without the signalling that is supposed to start the chain reaction.  So, the cell just keeps growing and dividing without control.

The trial you mention tests a new drug being developed by Glaxo SmithKline that inhibits BRAF.  The idea is that by doing this, they can shut down the cell growth.  Roche has a similar drug that is a bit further along in development and is showing a lot of promise.  It has response rates of over 60% but also does not generally result in a durable response.  This particular trial has two arms–the GSK BRAF inhibitor, and DTIC.  Patients are randomized into one or the other arm.

I hope this helps!

Tim–MRF

i am so sorry to hear what Craig is going through. I have been on the GSK2118436 Braf since September of 2010 at UCLA. I have multiple tumors and lesions throughout my left leg and into my pelvis. I have had a slow but steady decrease in the amount of mel in my leg since I started. It seems to shrink some tumors while ignoring another tumor that is right next to it. But no tumors have become bigger since I have been on it. I just had a CT this morning – so hopefully things are still progressing positivley.

the side effects have been manageable…sore feet and hands and constant skin things erupting that look like little warts that they keep removing every few weeks.  I hope Craig responds well and if you have any questions you can email me direct [email protected]

Laurie

i am so sorry to hear what Craig is going through. I have been on the GSK2118436 Braf since September of 2010 at UCLA. I have multiple tumors and lesions throughout my left leg and into my pelvis. I have had a slow but steady decrease in the amount of mel in my leg since I started. It seems to shrink some tumors while ignoring another tumor that is right next to it. But no tumors have become bigger since I have been on it. I just had a CT this morning – so hopefully things are still progressing positivley.

the side effects have been manageable…sore feet and hands and constant skin things erupting that look like little warts that they keep removing every few weeks.  I hope Craig responds well and if you have any questions you can email me direct [email protected]

Laurie