Gleevec/Taxol for Patients With Uterine Papillary Serous Carcinoma
- To determine the maximum tolerated dose (MTD) of imatinib mesylate in combination with fixed dose paclitaxel in patients with stage IIIC, IV or recurrent uterine papillary serous carcinoma.
- To determine the nature and degree of toxicity of imatinib mesylate and paclitaxel in this cohort of patients.
- To determine the efficacy of imatinib mesylate and paclitaxel in patients with stage IIIC, IV or recurrent uterine papillary serous carcinoma whose tumor expresses either c-Kit, PDGFR or abl.
|Uterine Cancer||Drug: Imatinib Mesylate Drug: Paclitaxel||Phase 1 Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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)|
- Maximum Tolerated Dose (MTD) of Imatinib Mesylate in Combination with Fixed Dose Paclitaxel [ Time Frame: Evaulated with each 3 week cycle ]MTD is highest dose level in which 6 participants treated with at most 2 experiencing dose limiting toxicity (DLT). Study utilizes Common Terminology for Adverse Events Criteria (CTCAE) version 3.0 for adverse event reporting.
- Efficacy of Gleevec and Taxol in Participants with Stage IIIC, IV or Recurrent Uterine Papillary Serous Carcinoma Whose Tumor Expresses Either c-KIT, PDGFR, Abl [ Time Frame: 6 weeks ]
Efficacy defined by duration of response (time to tumor progression for participants with measurable disease) and disease-free interval (duration of response for those with non-measurable disease). Response duration measured from time of response (not the beginning of treatment) until there is evidence of progressive disease. Time to treatment failure also be measured in responding patients.
Evaluation of tumor response (for participants who already have the disease) determined by CT scan or MRI and chest x-ray (patients with chest disease).
|Study Start Date:||December 2003|
|Primary Completion Date:||April 2015 (Final data collection date for primary outcome measure)|
Experimental: Paclitaxel + Imatinib Mesylate
Phase I, Phase II (Arm 2) = Paclitaxel + Imatinib Mesylate
Drug: Imatinib Mesylate
Phase I = 400 mg by mouth daily
Phase II (Arm 2) = 400 mg by mouth daily
Other Names:Drug: Paclitaxel
175 mg/m^2 by vein Over 3 Hours Every 21 Days
Other Name: Taxol
Phase II, (Arm 1) = Paclitaxel
175 mg/m^2 by vein Over 3 Hours Every 21 Days
Other Name: Taxol
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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 cancer.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00506779
|United States, Texas|
|University of Texas MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Study Chair:||Judith Wolf, MD||M.D. Anderson Cancer Center|
|Principal Investigator:||Brian M. Slomovitz, MD||M.D. Anderson Cancer Center|