Cabozantinib (XL184) clinical trial

LaundryQueen

Thanks to Greg (gdpawel), I found this promising targeted therapy phase II clinical trial (identifier number NCT00940225) which may be of interest to some OVCA survivors who have had their second recurrence. I am not eligible because the inclusion criteria requires that the subject has failed on their second line of chemo & I haven't been that far around the block yet.

The drug is given by mouth & the main side effect is nausea--the dosage is lowered if nausea is problematic. The drug was discovered as a cancer treatment accidentally--the researchers were looking for an anti-inflammatory drug to treat inflammatory bowel diseases. The drug is a PPAR-gamma modulator (that's the pathway it modulates). Because healthy epithelial cells die easily when kept in a culture for experimental use, malignant epithelial cells are used for experiments. The researcher accidentally overdosed the malignant epithelial cells & they all died!

So Cabo is now in clinical trials as an epithelial cancer targeted therapy. Currently, they are enrolling only ovarian & prostate cancer patients. I imagine our UPSC sisters who are in their second recurrence may be interested in watching out for the phase III trials.

NCEllen

Clinical trial hopeful
for my husband who is fighting advanced prostate cancer that has mets to the bone. XL184 has been shown to reduce bone lesions. Because he had a small lung embolism this past Jan. he's had to wait a year to get on this trial, but is currently on another clinical trial for the next two months. He's being followed at Duke and will be able to roll-over to the XL184 in Jan. if he can overcome his advanced symptoms (lots of bone pain and fatigue). I had noticed that this was used for ovarian cancer as well. I'm currently on a Phase II clinical trial OSI 906-202 that is a glucose inhibitor with the thinking it will kill glulcose receptive tumors. I've had some EKG abnormalities - so yet to be seen if I can stay on this trial. I have dose dense Taxol weekly and my numbers are down, but the CT is the real indicator- we'll see 'bout that next week. I suppose my main point is that the trials and research continue and that is a gift for us. Someday there will be a cure. But also we are the recipients of the gift of choices - especially the choice to have quality, enjoyment, peace and comfort in life within the lifetime we are all given. Hugs- Peace and Constant thoughts of you all - Ellen

LaundryQueen

NCEllen said:

Clinical trial hopeful
for my husband who is fighting advanced prostate cancer that has mets to the bone. XL184 has been shown to reduce bone lesions. Because he had a small lung embolism this past Jan. he's had to wait a year to get on this trial, but is currently on another clinical trial for the next two months. He's being followed at Duke and will be able to roll-over to the XL184 in Jan. if he can overcome his advanced symptoms (lots of bone pain and fatigue). I had noticed that this was used for ovarian cancer as well. I'm currently on a Phase II clinical trial OSI 906-202 that is a glucose inhibitor with the thinking it will kill glulcose receptive tumors. I've had some EKG abnormalities - so yet to be seen if I can stay on this trial. I have dose dense Taxol weekly and my numbers are down, but the CT is the real indicator- we'll see 'bout that next week. I suppose my main point is that the trials and research continue and that is a gift for us. Someday there will be a cure. But also we are the recipients of the gift of choices - especially the choice to have quality, enjoyment, peace and comfort in life within the lifetime we are all given. Hugs- Peace and Constant thoughts of you all - Ellen

Thanks for your response--I
Thanks for your response--I am interested in hearing about your husband's experience with this trial in the future. Ovarian & prostate cancers seem to share similar characteristics & treatments. I might just check in on the prostate discussion board...

gdpawel

LaundryQueen said:

Thanks for your response--I
Thanks for your response--I am interested in hearing about your husband's experience with this trial in the future. Ovarian & prostate cancers seem to share similar characteristics & treatments. I might just check in on the prostate discussion board...

Cabozantinib
Queen

What I personally like about Cabozantinib is they can finally put Taxol to rest (like in its grave).

They were looking for drugs to treat the inflammation seen in Crohn's disease and ulcerative colitis. They tested this PPAR-gamma modulator. It would never normally have been thought of as a cancer drug, or in fact a drug of any kind. They ran several tests and found the compound killed pretty much every epithelial tumor cell lines they have seen. Epithelial cells line organs such as the colon, and also make up skin.

They reported in the journal International Cancer Research that it killed colon tumors in mice without making the mice sick. The compound worked in much the same way as the taxane drugs, including Taxol, which were originally derived from Pacific yew trees. It targets part of the cell cytoskeleton called tubulin. Tubulin is used to build microtubules, which in turn make up the cell's structure.

Destroying it kills the cell, but cancer cells eventually evolve mechanisms to pump out the drugs that do this, a problem called resistance. Resistance to anti-tubulin therapies, like Taxol, is a huge problem in many cancers. They see this as another way to get to the tubulin. The PPAR-gamma compound does this in a different way from the taxanes, which might mean it could overcome the resistance that tumor cells often develop to chemotherapy.

Most of the drugs like Taxol affect the ability of tubulin to form into microtubules. This doesn't do that -- it causes the tubulin itself to disappear. They do not know why. They planned to do more safety tests. As the compound is already patented, the team will probably have to design something slightly different to be able to patent it as a new drug.

And NCEllen, Cabozantinib may reduce or eliminate bone metastases in some patients. The results were presented at the 2011 annual meeting at ASCO. Several types of cancer, including prostate, have a tendency to spread to the bone.

Greg

LaundryQueen

gdpawel said:

Cabozantinib
Queen

What I personally like about Cabozantinib is they can finally put Taxol to rest (like in its grave).

They were looking for drugs to treat the inflammation seen in Crohn's disease and ulcerative colitis. They tested this PPAR-gamma modulator. It would never normally have been thought of as a cancer drug, or in fact a drug of any kind. They ran several tests and found the compound killed pretty much every epithelial tumor cell lines they have seen. Epithelial cells line organs such as the colon, and also make up skin.

They reported in the journal International Cancer Research that it killed colon tumors in mice without making the mice sick. The compound worked in much the same way as the taxane drugs, including Taxol, which were originally derived from Pacific yew trees. It targets part of the cell cytoskeleton called tubulin. Tubulin is used to build microtubules, which in turn make up the cell's structure.

Destroying it kills the cell, but cancer cells eventually evolve mechanisms to pump out the drugs that do this, a problem called resistance. Resistance to anti-tubulin therapies, like Taxol, is a huge problem in many cancers. They see this as another way to get to the tubulin. The PPAR-gamma compound does this in a different way from the taxanes, which might mean it could overcome the resistance that tumor cells often develop to chemotherapy.

Most of the drugs like Taxol affect the ability of tubulin to form into microtubules. This doesn't do that -- it causes the tubulin itself to disappear. They do not know why. They planned to do more safety tests. As the compound is already patented, the team will probably have to design something slightly different to be able to patent it as a new drug.

And NCEllen, Cabozantinib may reduce or eliminate bone metastases in some patients. The results were presented at the 2011 annual meeting at ASCO. Several types of cancer, including prostate, have a tendency to spread to the bone.

Greg

Big sigh...
Greg: too bad I'm not eligible for the clinical trial. I would have to have failed on topotecan or doxil first--neither one of those are my best option at this time either. The doc said if the trials go well, Cabo could be on the market in 3-4 years. Hmpf, I don't know if I'll be still around but one can always hope.