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

NCT ID: NCT00091377

Last Updated: 2016-07-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-08-31
• Study Completion Date: 2008-03-31

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.

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.

Conditions

Fallopian Tube Cancer; Ovarian Cancer; Primary Peritoneal Cavity Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

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

Group Type: EXPERIMENTAL

cisplatin

Intervention Type: DRUG

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

phenoxodiol

Intervention Type: DRUG

IV 3 mg/kg

Arm B

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

Group Type: EXPERIMENTAL

paclitaxel

Intervention Type: DRUG

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

phenoxodiol

Intervention Type: DRUG

IV 3 mg/kg

Interventions

cisplatin

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

Intervention Type: DRUG

paclitaxel

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

Intervention Type: DRUG

phenoxodiol

IV 3 mg/kg

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

MEI Pharma, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Warren Lancaster

Role: STUDY_CHAIR

Kazia Therapeutics Limited

Locations

Yale Comprehensive Cancer Center at Yale University School of Medicine

New Haven, Connecticut, United States

Royal Women's Hospital

Carlton, Victoria, Australia

Countries

United States; Australia

References

Kelly MG, Mor G, Husband A, O'Malley DM, Baker L, Azodi M, Schwartz PE, Rutherford TJ. Phase II evaluation of phenoxodiol in combination with cisplatin or paclitaxel in women with platinum/taxane-refractory/resistant epithelial ovarian, fallopian tube, or primary peritoneal cancers. Int J Gynecol Cancer. 2011 May;21(4):633-9. doi: 10.1097/IGC.0b013e3182126f05.

Reference Type: RESULT

PMID: 21412168 (View on PubMed)

Other Identifiers

NOVOGEN-NV06-037

Identifier Type: -

Identifier Source: secondary_id

YALE-HIC-26423

Identifier Type: -

Identifier Source: secondary_id

CDR0000389129

Identifier Type: -

Identifier Source: org_study_id