Phenoxodiol Combined With Either Cisplatin or Paclitaxel in Patients With Recurrent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as cisplatin and paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Phenoxodiol may help cisplatin and paclitaxel kill more tumor cells by making tumor cells more sensitive to the drugs. PURPOSE: This randomized phase I/II trial is studying the side effects of phenoxodiol when given together with either cisplatin or paclitaxel and to see how well they work in treating patients with recurrent late-stage ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer that has not responded to treatment with drugs such as paclitaxel, docetaxel, cisplatin, or carboplatin.

Detailed Description
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OBJECTIVES: Primary Compare the safety and tolerability of phenoxodiol combined with cisplatin or paclitaxel in patients with recurrent late-stage ovarian epithelial, fallopian tube, or primary peritoneal cancer that is refractory or resistant to platinum and/or taxane drugs. Compare, preliminarily, tumor response in patients treated with these regimens. OUTLINE: This is an open-label, randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms according to medical history. Arm I: Patients receive phenoxodiol IV over 10 minutes on days 1 and 2 and cisplatin IV over 1 hour on day 2. Arm II: Patients receive phenoxodiol as in arm I and paclitaxel IV over 1 hour on day 2. In both arms, treatment repeats every 6 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at 12, 24, 36, and 48 weeks or at the end of study participation. Patients are followed at 6 and 12 months. PROJECTED ACCRUAL: A total of 40 patients (20 per treatment arm) will be accrued for this study.

Official Title
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Multi-Center, Phase Ib/IIa Safety and Preliminary Efficacy Study of Phenoxodiol (Intravenous) as a Chemo-Sensitizing Agent for Cisplatin and Paclitaxel in Epithelial Ovarian Cancer or Primary Peritoneal Cancer, Platinum- and/or Taxane-Refractory or Resistant

Conditions
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Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cavity Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: paclitaxel
* Drug: phenoxodiol


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal cancer Recurrent disease Received no more than 4 prior chemotherapy regimens for this malignancy Considered refractory or resistant to prior taxane (paclitaxel or docetaxel) and/or platinum (cisplatin or carboplatin) therapy based on 1 of the following criteria: Treatment-free interval < 6 months after platinum or paclitaxel Disease progression during platinum- or paclitaxel-based therapy Measurable or evaluable disease Measurable disease is defined as at least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan Evaluable disease is defined as doubling of CA 125 blood levels within the past 6 months AND CA 125 level ≥ 2 times upper limit of normal (ULN) within the past week No active CNS metastases Patients with known CNS metastases must have received prior radiotherapy or CNS-directed chemotherapy AND have ≥ 4 weeks of stable disease PATIENT CHARACTERISTICS: Age Over 18 Performance status Karnofsky 60-100% Life expectancy At least 3 months Hematopoietic Neutrophil count > 1,500/mm^3 Platelet count > 100,000/mm^3 WBC > 3,000/mm^3 Hematocrit ≥ 28% (transfusion or growth factors allowed) Hemoglobin > 8.0 g/dL (transfusion or growth factors allowed) Hepatic Bilirubin ≤ 1.5 times ULN SGOT ≤ 2.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN Renal Creatinine ≤ 1.5 times ULN Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active infection requiring antibiotics No neuropathy (sensory or motor) > grade 1 PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent immunotherapy Chemotherapy See Disease Characteristics No other concurrent chemotherapy Endocrine therapy No concurrent hormonal therapy for the malignancy Radiotherapy See Disease Characteristics No prior whole abdominal radiotherapy Concurrent localized radiotherapy allowed for control of local complications not indicative of general disease progression Surgery Not specified Other Recovered from prior antineoplastic therapy More than 4 weeks since prior standard therapy for malignant tumor More than 6 months since prior investigational anticancer drugs No other concurrent investigational drugs No concurrent drugs significantly metabolized by the cytochrome P450 enzymes CYP2C8, CYP2C9, CYP2C19, and CYP3A4/B1C No concurrent amifostine or other protective agents No concurrent grapefruit juice

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Phenoxodiol IV 3 mg/kg combined with cisplatin 40 mg/m2 on Day 2 6 week cycles | Drug: cisplatin<br>* IV 40 mg/m2 on Day 2 Number of Cycles: until progression or unacceptable toxicity or other withdrawal criteria are met.<br>Drug: phenoxodiol<br>* IV 3 mg/kg<br>|
| Experimental: Arm B<br>Phenoxodiol IV 3 mg/kg combined with paclitaxel 80 mg/m2 on Day 2 6 week cycles | Drug: paclitaxel<br>* IV 80 mg/m2 on Day 2 Number of Cycles: until progression or unacceptable toxicity or other withdrawal criteria are met.<br>Drug: phenoxodiol<br>* IV 3 mg/kg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability |  | Average 6 mo | 
| Efficacy |  | Average 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Surrogate marker of tumor response in terms of plasma protein tNOX |  | Average 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent ovarian epithelial cancer, fallopian tube cancer, primary peritoneal cavity cancer