A Phase I/II Study of Gleevec/Taxol in Patients With Newly Diagnosed Stage IIIC or IV or Recurrent (Any Stage) Uterine Papillary Serous Carcinoma (UPSC)
Before possible study participants can receive treatment with imatinib mesylate and
paclitaxel, their tumor tissue that was previously collected (at the surgery to diagnose
your tumor) will be tested for the following three biomarkers: c-Kit, PDGFR-B, and Abl.
Those participants who have at least one positive biomarker will be eligible for treatment
on this study.
Paclitaxel is a chemotherapy drug used in the treatment of ovarian cancer. Imatinib mesylate
is a medication that blocks several proteins that are important in the development of
Before treatment starts, you will have a complete physical exam, routine blood tests (about
2-3 teaspoons), an electrocardiogram (ECG--a test to measure the electrical activity of the
heart). You will have an echocardiogram (an ultrasound test used to visualize the
structures of the heart), a chest x-ray, and a CT scan or MRI of the abdomen and pelvis.
Women who are able to have children must have a negative blood pregnancy test.
Routine blood tests (about 2 teaspoons) will be done weekly during treatment, and before
each course of therapy, which is every 3 weeks. A complete checkup including evaluation of
side effects, will also be done before each course of therapy and at the end of therapy (3
weeks after treatment ends).
There are two phases to this study, Phase I and Phase II. If you are assigned to Phase 1,
you will receive treatment with imatinib mesylate and paclitaxel. Phase 1 will study 3
different doses of imatinib mesylate in combination with a fixed dose of paclitaxel. The
Phase I part of the study will help researchers learn the most effective dose of imatinib
mesylate to be used in combination with paclitaxel. All participants in Phase 1 will
receive one of three doses of imatinib mesylate to be given with a standard dose of
paclitaxel. You will be assigned to a specific dose level based on the number of
participants treated at the time of your enrollment.
The Phase II portion of the study will begin only after the most effective dose of imatinib
mesylate has been determined.
If you are assigned to Phase II, you will be randomly assigned (as in the toss of a coin) to
one of two treatment groups. Participants in one group will receive treatment with
paclitaxel only (every 21 days). Participants in the second group will receive treatment
with paclitaxel (every 21 days) along with imatinib mesylate (every day). The dose level of
imatinib mesylate that you receive will be the same as the dose used during Phase I. The
computer-generated assignment will favor the treatment group which is more effective. For
example, if the combination of paclitaxel and imatinib mesylate is more effective than
paclitaxel alone, then more patients will be selected to receive the combination therapy.
You will receive paclitaxel by vein over 3 hours every 21 days. Those participants who are
assigned treatment with both paclitaxel and imatinib mesylate will begin taking imatinib
mesylate the day after the first dose of paclitaxel. A single dose of imatinib mesylate
will be taken by mouth every day.
Evaluation of tumor response (for participants who already have the disease) will be
determined by CT scan or MRI and chest x-ray (patients with chest disease). These scans
will be taken after Courses 2 and 4 , then after every 3 courses until the therapy is
finished, and once more at the end of therapy. Patients who show no signs of the disease
will be given a total of up to 6 courses. Patients who have the disease may continue
treatment until the disease gets worse. You will be taken off study if the disease gets
worse or intolerable side effects occur. If you are removed from the study, you will be
asked to have a follow-up CT scan or MRI and chest x-ray to evaluate the tumor.
THIS IS AN INVESTIGATIONAL STUDY. Paclitaxel is commercially available and approved for use
in the treatment of ovarian cancer. Gleevec® is also commercially available and approved
for use in the treatment of certain types of adult leukemias and stomach cancers. The
combination of paclitaxel and imatinib mesylate is still investigational and has been
approved for use in research only.
At least 51 and as many as 65 participants will take part in this study. All participants
will be enrolled and treated at M. D. Anderson.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD) of imatinib mesylate in combination with fixed dose paclitaxel
Evaulated with each 3 week cycle
David M. Gershenson, MD,BA
UT MD Anderson Cancer Center
United States: Institutional Review Board
|UT MD Anderson Cancer Center||Houston, Texas 77030|