Gleevec/Taxol for Patients With Uterine Papillary Serous Carcinoma
Uterine Cancer
About this trial
This is an interventional treatment trial for Uterine Cancer focused on measuring Uterine Papillary Serous Carcinoma, Uterine Cancer, UPSC, Taxol, Paclitaxel, Gleevec, Imatinib Mesylate, STI571
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed newly diagnosed (stage IIIC or IV) or recurrent (any stage) uterine papillary serous carcinoma. Patients with recurrent disease may not have been treated with taxanes in the past.
- Patients may not receive concurrent radiotherapy while participating in this protocol.
- Patients may have measurable or non-measurable disease.
- Patients may have mixed endometrioid or clear cell components in addition to the serous histology.
- Patients' tumor tissue must express one or more of the following biomarkers: c-Kit, PDGFR-B, or Abl. Positivity will be defined as 2+/3+ intensity in at least 10% of the tumor.
- Patients must have pretreatment granulocyte count (i.e. segmented neutrophils and bands) of >/= 1,500/Fl, a hemoglobin level of >/= 9.0 gm/dl, and a platelet count of >/= 100,000/Fl.
- Patients must have an adequate renal function as documented by serum creatinine of </=2.0 mg/dl.
- Patients must have adequate hepatic function as documented by a serum bilirubin </=1.5mg/dl, regardless of whether patients have liver involvement secondary to tumor. Alanine aminotransferase (SGPT) and aspartate aminotransferase (SGOT) must be </=2.5x institutional upper limit of normal unless the liver is involved with tumor, in which case levels must be </=5x institutional upper limit of normal.
- Zubrod performance status of 0, 1, or 2.
- Patients should not have received prior chemotherapy or radiation (except palliative radiation) within the last 30 days.
- Patients must have signed informed consent indicating that they are aware of the investigational nature of this study.
Exclusion Criteria:
- Patients who have previously received imatinib mesylate or taxanes.
- Patients with any active or uncontrolled systemic infection, including known HIV infection.
- Patients with psychiatric disorders that would interfere with consent or follow-up.
- Patients with New York Heart Association (NYHA) Class III/IV congestive heart failure, unstable angina or a history of myocardial infarction within the previous 6 months.
- Patients with a history of prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for at least three years.
- Oxygen-dependent lung disease.
- Patients in whom corticosteroids are contraindicated.
- Uncontrolled severe hypertension or uncontrolled diabetes mellitus.
- Presence of clinically apparent central nervous system metastases or carcinomatous meningitis.
- Patients with any form of chronic liver disease.
- Patients with a history of seizures are ineligible. Patients receiving phenytoin, phenobarbital, or other anti-epileptic prophylaxis are ineligible.
- Patients with any other severe concurrent disease, which in the judgment of the investigator, would make the patient inappropriate for entry into this study, including significant hepatic, renal, or gastrointestinal diseases.
- Patients with a deep venous or arterial thrombosis (including pulmonary embolism) within 6 weeks of study entry.
- Patients who are receiving therapeutic doses of warfarin or any blood thinning agent.
- Patients with a history of non-compliance with medical regimens or who are considered potentially unreliable.
- Pregnant or lactating women. Women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
Sites / Locations
- University of Texas MD Anderson Cancer Center
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Phase I: Paclitaxel + Imatinib Mesylate
Phase II: Paclitaxel Alone or Pacliataxel + Imatinib Mesylate
Phase I MTD using oral dose Imatinib Mesylate escalation 400, 500, 600 mg daily; Paclitaxel 175 mg/m^2 every 21 days
Intended randomization of Paclitaxel alone or Paclitaxel + Imatinib Mesylate; the study was terminated early due to poor enrollment and all patients are no longer being treated or followed. Single treatment arm MTD using oral dose Imatinib Mesylate escalation = 500 mg daily; Paclitaxel 175 mg/m^2 every 21 days Phase II, (Arm 1) = Paclitaxel 175 mg/m^2 every 21 days Phase II, (Arm 2) Paclitaxel 175 mg/m^2 every 21 days+ Imatinib Mesylate MTD using oral dose Imatinib Mesylate escalation = 500 mg daily