Imatinib Mesylate in Treating Patients With Persistent or Recurrent Ovarian Epithelial or Primary Peritoneal Cancer

Study Overview
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Brief Summary
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Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have persistent or recurrent ovarian epithelial or primary peritoneal cancer. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the cytostatic, anti-tumor activity of Gleevec (Imatinib Mesylate) through the probability of surviving progression-free for at least 6 months in patients with recurrent or persistent epithelial ovarian or primary peritoneal carcinoma receiving Gleevec. II. To determine the frequency and severity of adverse effects of Gleevec in this cohort of patients as assessed by CTC. SECONDARY OBJECTIVES: I. To determine the distribution of the overall survival. II. To determine the distribution of progression-free survival. III. To estimate the clinical response rate (partial and complete response as defined under the RECIST criteria). IV. To assess the effects of prognostic variables: initial performance status, platinum sensitivity, and mucinous (or clear cell) histology). TERTIARY OBJECTIVES: I. To determine the levels of expression of c-KIT and its ligand, stem cell factor (SCF) in archived, formalin fixed, paraffin embedded primary tumors collected prior to the initiation of first-line chemotherapy. II. To determine the levels of expression of platelet derived growth factor receptor (PDGFR) and its ligand PDGF in archived, formalin fixed, paraffin embedded primary tumors collected prior to the initiation of first-line chemotherapy. III. To determine the levels of expression of AKT2 and its activated form, phospho-AKT2, in archived, formalin fixed, paraffin embedded primary tumors collected prior to the initiation of first-line chemotherapy. OUTLINE: This is a multicenter study. Patients receive oral imatinib mesylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Official Title
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A Phase II Evaluation Of Gleevec (Imatinib Mesylate) (IND #61135, NSC #716051) In The Treatment Of Persistent Or Recurrent Epithelial Ovarian Or Primary Peritoneal Carcinoma

Conditions
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Primary Peritoneal Cavity Cancer, Recurrent Ovarian Epithelial Cancer

Intervention / Treatment
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* Drug: imatinib mesylate
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed ovarian epithelial or primary peritoneal carcinoma Recurrent or persistent disease At least 1 unidimensionally measurable target lesion At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan Tumors within a previously irradiated field considered nontarget lesions At least one prior platinum-based chemotherapy regimen (containing carboplatin, cisplatin, or another organoplatinum compound) for primary disease required Initial treatment may include high-dose, consolidation, or extended therapy Initial treatment-free interval less than 12 months for patients who received only 1 prior platinum-based regimen Initial treatment-free interval of more than 12 months allowed provided disease progression has occurred within 12 months after retreatment with a second-line platinum-based regimen Ineligible for a higher priority GOG protocol (e.g., any active phase III GOG protocol for the same patient population) Performance status - GOG 0-2 (if patient has received one prior treatment regimen) Performance status - GOG 0-1 (if patient has received two prior treatment regimens) Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT/SGPT no greater than 2.5 times ULN Alkaline phosphatase no greater than 2.5 times ULN Creatinine no greater than 1.5 times ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception during and for 3 months after study participation No active infection requiring antibiotics No greater than grade 1 sensory and motor neuropathy No other invasive malignancy within the past 5 years except nonmelanoma skin cancer No signs or symptoms of bowel dysfunction At least 3 weeks since prior immunologic therapy directed at the malignant tumor No concurrent biologic therapy or immunotherapy for the malignant tumor Recovered from prior chemotherapy No prior noncytotoxic chemotherapy for persistent or recurrent disease One additional cytotoxic regimen for persistent or recurrent disease allowed No concurrent chemotherapy for the malignant tumor At least 1 week since prior hormonal therapy directed at the malignant tumor No concurrent therapeutic corticosteroids No concurrent anticancer hormonal therapy Concurrent hormone replacement therapy allowed Recovered from prior radiotherapy No prior radiotherapy to more than 25% of marrow-bearing areas No concurrent anticancer radiotherapy Recovered from recent prior surgery At least 3 weeks since other prior therapies directed at the malignant tumor No prior imatinib mesylate No prior anticancer therapy that would preclude study participation No concurrent therapeutic anticoagulation with warfarin No other concurrent investigational drugs No concurrent amifostine or other protective reagents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (imatinib mesylate)<br>Patients receive oral imatinib mesylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: imatinib mesylate<br>* Given PO<br>* Other names: Glivec;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | At 6 months | 
| Frequency and severity of adverse effects as assessed by CTC |  | Up to 7 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of overall survival |  | Up to 7 years | 
| Duration of progression-free survival |  | Up to 7 years | 
| Frequency of clinical response (partial and complete response) |  | Up to 7 years | 
| Prognostic variables: initial performance status, age, platinum sensitivity, and mucinous (or clear cell) histology |  | Baseline |