3-AP and Cisplatin in Treating Patients With Recurrent or Persistent Platinum-Resistant Ovarian Epithelial or Primary Peritoneal Cancer

Study Overview
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Brief Summary
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Drugs used in chemotherapy, such as 3-AP and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. This phase II trial is studying how well giving 3-AP together with cisplatin works in treating patients with recurrent or persistent platinum-resistant ovarian epithelial cancer or primary peritoneal cancer

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the antitumor activity of 3-AP and cisplatin in patients with recurrent or persistent platinum-resistant ovarian epithelial or primary peritoneal cancer. II. Determine the toxicity of this regimen in these patients. SECONDARY OBJECTIVES: I. Determine the duration of progression-free survival and overall survival in patients treated with this regimen. II. Determine the effects of prognostic variables, including initial performance status, age, and mucinous (or clear cell) histology, in these patients. OUTLINE: This is a non-randomized study. Patients receive 3-AP IV over 2 hours on days 1-4 and cisplatin IV over 1 hour on days 2 and 3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed for 5 years. PROJECTED ACCRUAL: A total of 23-48 patients will be accrued for this study within 13 months.

Official Title
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A Phase II Evaluation Of Triapine (NCI-Supplied Agent: NSC #663249, IND #68338) In Combination With Cisplatin (Commercially Available: NSC # 119875) In The Treatment Of Recurrent Or Persistent Platinum-Resistant Ovarian Or Primary Peritoneal Carcinoma

Conditions
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Primary Peritoneal Cavity Cancer, Recurrent Ovarian Epithelial Cancer, Stage III Ovarian Epithelial Cancer, Stage IV Ovarian Epithelial Cancer

Intervention / Treatment
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* Drug: triapine
* Drug: cisplatin
* 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 cancer 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 Outside a previously irradiated field Received 1 prior platinum-based chemotherapy regimen (e.g., carboplatin, cisplatin, or other organoplatinum compound) for primary disease Initial treatment may have included high-dose, consolidation, or extended therapy after surgical or non-surgical assessment Considered platinum resistant or refractory, according to 1 of the following criteria: Treatment-free interval of less than 6 months after platinum-based therapy Disease progression during platinum-based therapy Ineligible for any higher priority GOG protocol Performance status - GOG 0-2 (for patients who received 1 prior treatment regimen) Performance status - GOG 0-1 (for patients who received 2 prior treatment regimens) Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN) Bilirubin ≤ 1.5 times ULN Creatinine ≤ 1.5 times ULN No serious cardiac disease No prior myocardial infarction No uncontrolled congestive heart failure No pulmonary disease requiring oxygen Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Neuropathy (sensory and motor) ≤ grade 1 No active infections requiring antibiotics No hearing impairment No known G6PD deficiency No other invasive malignancy within the past 5 years except nonmelanoma skin cancer At least 3 weeks since prior biologic or immunologic agents for malignant tumor One prior non-cytotoxic regimen (e.g., monoclonal antibodies, cytokines, or small-molecule inhibitors of signal transduction) allowed See Disease Characteristics One prior paclitaxel-containing regimen allowed No prior 3-AP No other prior cytotoxic chemotherapy for recurrent or persistent disease, including retreatment with initial chemotherapy regimens Recovered from prior chemotherapy At least 1 week since prior hormonal therapy for malignant tumor Concurrent hormone replacement therapy allowed No prior radiotherapy to more than 25% of marrow-bearing areas Recovered from prior radiotherapy Recovered from prior surgery No prior cancer therapy that contraindicates receiving study therapy

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 (triapine and cisplatin)<br>Patients receive 3-AP IV over 2 hours on days 1-4 and cisplatin IV over 1 hour on days 2 and 3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. | Drug: triapine<br>* Given IV<br>* Other names: OCX-191;Drug: cisplatin<br>* Given IV<br>* Other names: DDP;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 |
| --- | --- | --- |
| Frequency and duration of objective response assessed using RECIST criteria |  | Up to 5 years | 
| Frequency and severity of observed adverse effects assessed using CTCAE version 3.0 |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of progression-free survival |  | From study entry until disease recurrence, death or date of last contact, assessed up to 5 years | 
| Duration of overall survival |  | From study entry to death or date of last contact, assessed up to 5 years | 
| Prognostic variables (e.g., initial performance status, age, and mucinous [or clear cell] histology) |  | Up to 5 years |