A Phase I/II Open-Label Study TPI 287 in Combination With Temozolomide in Patients With Metastatic Melanoma
TPI 287 is designed to block tumors from growing by preventing cancer cells from dividing.
Temozolomide is designed to kill cancer cells by causing breaks in the DNA (genetic
material) of the cell.
If you are found to be eligible to take part in this study, you will be assigned to a study
group based on when you joined this study. Up to 8 groups of 6 participants will be
enrolled in the Phase I portion of the study, and up to 64 participants will be enrolled in
If you are enrolled in the Phase I portion, the dose of TPI 287 and temozolomide you receive
will depend on when you joined this study. The first group of participants will receive the
lowest dose level of TPI 287 and temozolomide. Each new group will receive a higher dose of
TPI 287 and temozolomide than the group before it, if no intolerable side effects were seen.
If any of these participants have a dose limiting toxicity, 6 additional participants will
be added at the same dose. If a dose limiting toxicity occurs again, the dose level below
this will be considered the maximum tolerated dose.
If any participant experiences a life threatening side effect, no additional participants
will be enrolled into that dose level and no higher doses will be given. An additional 3
participants will be treated at the dose level below the one with life threatening toxicity.
Once the maximum tolerated dose of the combination is found, Phase II of the study will
If you are enrolled in the Phase II portion, you will receive the drug combination at the
highest dose that was tolerated in the Phase I portion
Central Venous Catheter (CVC):
You will have a CVC placed. A CVC is a sterile, flexible tube that will be placed into a
large vein while you are under local anesthesia. Your doctor will explain this procedure to
you in more detail, and you will be required to sign a separate consent form for this
Study Drug Administration:
You will receive TPI 287 by vein over 1 hour (+/- 10 minutes) on Days 1, 8, and 15 (+/- 1
day) of each 28 day study cycle. Before you receive each dose of TPI 287, you will receive
dexamethasone, Benadryl (diphenhydramine), and Pepcid (famotidine) by vein to help prevent
allergic reaction. You will also receive drugs to prevent nausea and vomiting. Your vital
signs will be measured before and 30 minutes following the end of the infusion of TPI 287.
Your vitals will be measured more often, if needed.
You will take temozolomide tablets by mouth on Days 1-5 at bedtime. You should not eat for
at least 1 hour before and 1 hour after taking temozolomide.
Before each cycle, your performance status will be recorded and you will have a physical
exam. You will also be asked about any symptoms you may be experiencing and any drugs you
On Days 1, 8, and 14 of each cycle:
-Blood (about 1 teaspoon) will be drawn for routine tests before you receive TPI 287.
On Day 22 of each cycle:
-Blood (about 1 teaspoon) will be drawn for routine tests.
Every 8 weeks, you will have a CT scan or MRI scan to check the status of the disease. If
you have brain metastasis, you will have an MRI of the brain every 4 weeks. If you do not
have brain metastasis, you will have MRI of the brain every 8 weeks.
Length of Study:
You will continue taking the study drugs for as long as you are benefitting. You will be
taken off study if the disease gets worse or intolerable side effects occur.
About 4 weeks after you stop taking TPI 287 in combination with Temozolomide, you have an
end-of-study visit. At this visit, the following tests and procedures will be performed:
- You will have a physical exam.
- You will be asked about any complications or side effects you may be experiencing.
- Blood (about 2 tablespoons) will be drawn for routine tests.
- If your doctor thinks it is needed, you will have a CT scan or MRI scan to check the
status of the disease.
This is an investigational study. TPI 287 is not FDA approved or commercially available.
At this time, TPI 287 is being used in research only. Temozolomide is FDA approved and
commercially available for primary brain cancer. The use of temozolomide in combination
with TPI 287 is investigational.
Up to 106 patients will take part in this study. All patients will be enrolled at MD
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD)
28 day study cycle
Agop Y. Bedikian, MD, BS
UT MD Anderson Cancer Center
United States: Food and Drug Administration
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