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)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
研究概览
简要总结
Objectives:
- 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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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.
研究组 & 干预措施
Phase I: Paclitaxel + Imatinib Mesylate
Phase I MTD using oral dose Imatinib Mesylate escalation 400, 500, 600 mg daily; Paclitaxel 175 mg/m^2 every 21 days
干预措施: Imatinib Mesylate (Drug)
Phase I: Paclitaxel + Imatinib Mesylate
Phase I MTD using oral dose Imatinib Mesylate escalation 400, 500, 600 mg daily; Paclitaxel 175 mg/m^2 every 21 days
干预措施: Paclitaxel (Drug)
Phase II: Paclitaxel Alone or Pacliataxel + Imatinib Mesylate
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
干预措施: Imatinib Mesylate (Drug)
Phase II: Paclitaxel Alone or Pacliataxel + Imatinib Mesylate
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
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
时间窗: Evaluated at 3 weeks (one cycle)
Maximum Tolerated Dose (MTD) of Oral Imatinib Mesylate in Combination with Fixed Dose Paclitaxel where MTD of Imatinib Mesylate (mg/m\^2 daily) to be determined with conventional 3+3 design, 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. Following cohorts of 3 at lower dose levels until 1 of 3 patients experiences DLT; if 1 of 3 patients experiences DLT at dose level, enter 3 additional patients at dose level, if only 1 of 6 patients experiences DLT at dose level, proceed to next higher dose level with cohort of 3; If 2 of 3 or 3 of 6 patients experience DLT, MTD has exceeded. Once DLT exceeded, treat another 3 patients at previous dose if there were only 3 patients treated at that dose level. MTD is highest dose level in which treated 6 patients with at most 2 experiencing the DLT.
次要结局
- Time to Tumor Progression(Evaluation at at 6 weeks, tumor restaging continued up to 6 cycles (18 weeks) or until disease progression, whichever comes first)
- Number of Participants With Complete Response(6 weeks to 18 weeks; Best response achieved since study entry where measurable disease defined as => 1 lesion accurately measured in at least 1 dimension (longest dimension to be recorded))