Irofulven in Treating Patients With Recurrent or Persistent 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 irofulven in treating patients who have recurrent or persistent ovarian epithelial cancer or primary peritoneal cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

Detailed Description
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OBJECTIVES: I. Determine the antitumor activity of irofulven in patients with persistent or recurrent platinum-sensitive ovarian epithelial or primary peritoneal cancer. II. Determine the toxicity of this drug in these patients. OUTLINE: Patients receive irofulven IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression. Patients are followed at approximately 30 days, every 3 months for 2 years, and then every 6 months for 3 years. PROJECTED ACCRUAL: Approximately 22-60 patients will be accrued for this study within at least 6 months.

Official Title
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A Phase II Evaluation Of Irofulven (IND #55804, NSC #683863) In The Treatment Of Recurrent Or Persistent Platinium-Sensitive Ovarian Or Primary Peritoneal Cancer

Conditions
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Primary Peritoneal Cavity Cancer, Recurrent Ovarian Epithelial Cancer

Intervention / Treatment
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* Drug: irofulven


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* defined as: At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan Must have received 1 prior platinum-based chemotherapeutic regimen containing carboplatin, cisplatin, or another organoplatinum compound for primary disease Initial treatment may have included high-dose, consolidation, or extended therapy administered after surgical or non-surgical assessment Patients who have not received prior paclitaxel may receive a second regimen containing paclitaxel Ineligible for a higher priority GOG protocol (e.g., any active phase III GOG protocol for the same patient population) Platinum-sensitive disease Platinum-free interval** of more than 6 months, but less than 12 months duration, with no clinical evidence of progressive disease after response to platinum Performance status - GOG 0-2 for patients who received 1 prior therapy regimen Performance status - GOG 0-1 for patients who received 2 prior therapy 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 no greater than 2.5 times ULN Alkaline phosphatase no greater than 2.5 times ULN Creatinine normal Creatinine clearance at least 60 mL/min No prior congestive heart failure requiring medication No uncontrolled hypertension within the past 6 months Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other invasive malignancies within the past 5 years except nonmelanoma skin cancer No history of retinopathy and/or macular degeneration No neuropathy (sensory and motor) greater than grade 1 No active infection requiring antibiotics No other illness or condition that would preclude study entry No prior bone marrow or stem cell transplantation At least 3 weeks since prior biologic therapy or immunotherapy for malignant tumor One prior non-cytotoxic regimen (e.g., monoclonal antibodies, cytokines, or small-molecule signal transduction inhibitors) allowed See Disease Characteristics At least 3 weeks since prior chemotherapy and recovered No prior irofulven No additional prior cytotoxic chemotherapy for recurrent or persistent disease, including retreatment with initial chemotherapy regimens At least 1 week since prior hormonal therapy for malignant tumor Concurrent hormone replacement therapy allowed See Disease Characteristics At least 3 weeks since prior radiotherapy and recovered No prior radiotherapy to more than 25% of marrow-bearing areas Recovered from recent prior surgery At least 3 weeks since any other prior therapy for malignant tumor No prior anticancer treatment that would preclude study therapy One prior noncytotoxic cytostatic regimen for recurrent or persistent disease allowed

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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 (irofulven)<br>Patients receive irofulven IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression. | Drug: irofulven<br>* Given IV<br>* Other names: MGI-114;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response | Per Gynecologic Oncology Group(GOG) Response Evaluation Criteria in Solid Tumors(RECIST) Criteria: Complete Response is disappearance of all target and non-target lesions; Partial Response is at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable dimensions; Increasing Disease is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD or the appearance of new lesions within 8 weeks of study entry. Response is to be evaluated every 42 days for the first 6 months and every 6 months thereafter while the patient is receiving study treatment, then every 3 months for 2 years and every 6 months for the next 3 years until documented progression or death. | From entry into study until documented progression or death, assessed up to 5 years. | 
| Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 |  | Assessed every cycle while on treatment, 30 days after the last cycle of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Per Gynecologic Oncology Group(GOG) Response Evaluation Criteria in Solid Tumors(RECIST) Criteria, progression is defined as at least a 20% increase in the sum of longest dimesions(LD) of target lesions taking as reference the smallest sum LD or the appearance of new lesions within 8 weeks of study entry. | From entry into study to death or date of last contact, assessed up to 5 years |