A Phase I/II Open-Label Study of TPI 287 for Patients With Metastatic Melanoma
The Study Drug TPI 287 is designed to block tumors from growing by preventing cancer cells
from dividing, which may cause them to die.
Patient will be assigned to a study group based on when they join this study. Up to 4
groups of 3-6 participants will be enrolled in the Phase I portion of the study, and up to
64 participants will be enrolled in Phase II.
If patient is enrolled in the Phase I portion, the dose of TPI 287 they receive will depend
on when they joined this study. The first group of participants will receive the lowest
dose level of TPI 287. Each new group will receive a higher starting dose of TPI 287 than
the group before it, if no intolerable side effects were seen. This will continue until the
highest tolerable dose of TPI 287 is found.
If patient is enrolled on one of the earlier dose levels, and they do not experience
intolerable side effects after 2 study cycles, their dose may be increased to the next
higher dose level that has been shown to be safe.
If patient has intolerable side effects, their dose may be lowered, paused, or stopped
completely. This will be up to their doctor.
If patient is enrolled in the Phase II portion, they will receive TPI 287 at the highest
dose that was tolerated in the Phase I portion.
Study Drug Administration:
Each study cycle is about 28 days (+/- 3 days).
TPI 287 will be given by vein over about 1 hour, on Days 1, 8, and 15 (+/- 2 days) of each
Since TPI 287 does not mix well in water, patient will receive doses of TPI 287 that have
been dissolved in cremophor. Cremophor is a chemical that is created from castor oil. Some
participants may be allergic to cremophor. Before patient receives each dose of TPI 287,
they will receive dexamethasone, Benadryl (diphenhydramine), and Pepcid (famotidine) by
vein, to help prevent allergic reaction. Each of these medications will be given over about
10 minutes. Patient will also receive drugs to prevent nausea and vomiting. The study
staff will tell patient more about these drugs and the risks for them.
At all study visits, patient will be asked about any symptoms they may be having and any
drugs they may be taking.
On Days 1, 8, 15, and 21 of each cycle, blood (about 1 teaspoon) will be drawn for routine
tests. The blood sample on Day 21 may be drawn at a clinic near patient's home. The study
staff will give patient more information about this.
On Day 28 of each cycle:
- Patient will have a physical exam, including measurement of their height, weight, and
- Patient's performance status will be recorded.
- Blood (about 1 teaspoon) will be drawn for routine tests.
- If the doctor thinks it is needed, patient will have an MRI scan of the brain to check
the status of the disease.
- If the doctor thinks it is needed, patient will have a neurological exam.
On Day 1 of Cycle 2 and then every other cycle after that (Cycles 2, 4, 6, and so on),
patient will have a CT scan of their chest, abdomen, and pelvis to check the status of the
Every 8 weeks, patient will have a CT or MRI scan of the brain to check the status of the
disease. If patient has brain metastasis, they will have a CT or MRI scan every 4 weeks.
Length of Study:
Patient may continue taking the study drug for up to 6 months. Treatment beyond 6 months
will be decided by patient's doctor. Patient will be allowed to continue taking the study
drug for as long as the doctor thinks it is in their best interest. Patient will no longer
be able to take the study drug if the disease gets worse, if intolerable side effects occur,
or if they are unable to follow study directions.
Patient's participation on the study will be over once they have completed the
end-of-treatment visit and follow-up.
About 4 weeks after patient stops receiving TPI 287, they will have an end-of-treatment
visit. At this visit, the following tests and procedures will be performed:
- Patient will have a physical exam, including measurement of their weight and vital
- Patient's performance status will be recorded.
- Patient will be asked about any problems or side effects they may be having.
- Blood (about 2 tablespoons) will be drawn for routine tests.
- If patient's doctor thinks it is needed, they will have a CT or MRI scan to check the
status of the disease.
- Patient will be contacted by phone or they will come in for a clinic visit. The phone
call should last about 5 minutes. Patient will be asked about any problems or side
effects they may be having:
- Every 2 months unless the disease gets worse.
- Then, every 3 months after that.
These follow-ups end 3 years after they enrolled in the study.
This is an investigational study. TPI 287 is not FDA approved or commercially available.
It is currently being used for research purposes only.
Up to 82 patients will take part in this study. All will be enrolled at M. D. Anderson.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD) TPI 287 administered weekly for three weeks out of every four in patients with metastatic melanoma
Optimal dose (MTD) of TPI 287 for the Phase II part of the study defined as level at which no dose limiting toxicities (DLTs) are experienced (3+3 dose escalation algorithm). DLT is defined as Grade 3 or higher toxicity that is reasonably likely to be associated with study treatment at 12 weeks.
With each 28 day cycle and DLTs at 12 weeks
Agop Y. Bedikian, MD, BS
UT MD Anderson Cancer Center
United States: Food and Drug Administration
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