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

Sponsor

MEI Pharma, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00091377

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

32.5

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Fallopian Tube Cancer Ovarian Cancer Primary Peritoneal Cavity Cancer	Drug: cisplatin Drug: paclitaxel Drug: phenoxodiol	Phase 1/Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

65 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 2004

Actual Primary Completion Date :

Dec 1, 2007

Actual Study Completion Date :

Mar 1, 2008

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Arm A

Phenoxodiol IV 3 mg/kg combined with cisplatin 40 mg/m2 on Day 2 6 week cycles

Drug: cisplatin

IV 40 mg/m2 on Day 2 Number of Cycles: until progression or unacceptable toxicity or other withdrawal criteria are met.

Drug: phenoxodiol

IV 3 mg/kg

Experimental: Arm B

Phenoxodiol IV 3 mg/kg combined with paclitaxel 80 mg/m2 on Day 2 6 week cycles

Drug: paclitaxel

IV 80 mg/m2 on Day 2 Number of Cycles: until progression or unacceptable toxicity or other withdrawal criteria are met.

Drug: phenoxodiol

IV 3 mg/kg

Outcome Measures

Primary Outcome Measures

Safety and tolerability [Average 6 mo]
Efficacy [Average 6 months]

Secondary Outcome Measures

Surrogate marker of tumor response in terms of plasma protein tNOX [Average 6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale Comprehensive Cancer Center at Yale University School of Medicine	New Haven	Connecticut	United States	06520-8028
2	Royal Women's Hospital	Carlton	Victoria	Australia	3053