Combination Chemotherapy Regimens in Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

NCT ID: NCT00028743

Last Updated: 2020-04-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 819 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-08-31
• Study Completion Date: 2013-01-10

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving the drugs in different combinations may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating ovarian epithelial, primary peritoneal, or fallopian tube cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of different combination chemotherapy regimens in treating patients who have stage IIB, stage III, or stage IV ovarian epithelial cancer , primary peritoneal cancer, or fallopian tube cancer.

Detailed Description

OBJECTIVES:

• Compare the efficacy of cisplatin and topotecan followed by paclitaxel and carboplatin vs paclitaxel and carboplatin only, in terms of time to disease progression, in patients with newly diagnosed stage IIB-IV ovarian epithelial, primary peritoneal, or fallopian tube cancer.
• Compare the overall survival of patients treated with these regimens.
• Compare the clinical objective response rates in patients with measurable disease at baseline treated with these regimens.
• Compare the toxic effects of these regimens in these patients.
• Compare the CA 125 normalization rates in patients treated with these regimens.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, age (65 years and under vs over 65 years), and pre-randomization surgery (no debulking vs debulking with macroscopic residual disease less than 1 cm vs debulking with macroscopic residual disease 1 cm or greater vs debulking with no macroscopic residual disease). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive cisplatin IV over 60 minutes on day 1 and topotecan IV over 30 minutes on days 1-5 of courses 1-4 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 of courses 5-8.
• Arm II: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 of courses 1-8.

In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Planned interval debulking surgery should occur after course 3 or 4.

Quality of life is assessed at baseline; on day 1 of courses 3, 5, and 7; at the end of the last course; and at 3 and 6 months after study treatment completion.

Patients are followed every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 800 patients (400 per treatment arm) will be accrued for this study within 2 years.

Conditions

Fallopian Tube Cancer; Ovarian Cancer; Peritoneal Cavity Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cisplatin, Topotecan, Paclitaxel plus Carboplatin

Arm 1

Group Type: ACTIVE_COMPARATOR

carboplatin

Intervention Type: DRUG

Arm 1 = 4 cycles vs Arm 2 = 8 cycles AUC5 (30 mins) day 1 of 21 day cycle

cisplatin

Intervention Type: DRUG

4 cycles 50mg/m2 (60 mins) day 1 of 21 day cycle

paclitaxel

Intervention Type: DRUG

Arm 1 = 4 cycles vs Arm 2 = 8 cycles 175mg/m2 (3 hours) day 1 of 21 day cycle

topotecan hydrochloride

Intervention Type: DRUG

4 cycles

.75mg/m2 (30 mins) days 1-5 of 21 day cycle

Paclitaxel plus Carboplatin

Arm 2

Group Type: ACTIVE_COMPARATOR

carboplatin

Intervention Type: DRUG

Arm 1 = 4 cycles vs Arm 2 = 8 cycles AUC5 (30 mins) day 1 of 21 day cycle

paclitaxel

Intervention Type: DRUG

Arm 1 = 4 cycles vs Arm 2 = 8 cycles 175mg/m2 (3 hours) day 1 of 21 day cycle

Interventions

carboplatin

Arm 1 = 4 cycles vs Arm 2 = 8 cycles AUC5 (30 mins) day 1 of 21 day cycle

Intervention Type: DRUG

cisplatin

4 cycles 50mg/m2 (60 mins) day 1 of 21 day cycle

Intervention Type: DRUG

paclitaxel

Arm 1 = 4 cycles vs Arm 2 = 8 cycles 175mg/m2 (3 hours) day 1 of 21 day cycle

Intervention Type: DRUG

topotecan hydrochloride

4 cycles

.75mg/m2 (30 mins) days 1-5 of 21 day cycle

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed stage IIB-IV ovarian epithelial, primary peritoneal, or fallopian tube cancer

• No borderline ovarian tumors
• Residual disease allowed
• Fine needle aspiration showing an adenocarcinoma is allowed instead of open or true-cut biopsy if the following are true:

• Presence of pelvic mass AND
• Omental cake or other metastasis larger than 2 cm in the upper abdomen unless proven stage IV disease AND
• Serum CA 125/carcinoembryonic antigen ratio at least 25 (if less than 25, a barium enema or colonoscopy and gastroscopy or radiological examination of the stomach should be negative for primary tumor within 6 weeks of study) AND
• Normal mammography within 6 weeks of study

PATIENT CHARACTERISTICS:

Age:

• 18 to 75

Performance status:

• ECOG 0-1

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Granulocyte count at least 2,000/mm^3
• Platelet count at least 150,000/mm^3

Hepatic:

• Not specified

Renal:

• Creatinine no greater than upper limit of normal

Cardiovascular:

• No clinically relevant atrial or ventricular arrhythmias
• No myocardial infarction (MI) within the past 6 months (pretreatment ECG as only evidence of MI allowed)
• No history of second- or third-degree heart blocks unless pacemaker implanted
• History of first-degree heart block allowed

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No complete bowel obstruction
• No prior allergic reaction to drugs containing Cremophor EL or compounds chemically related to study drugs
• No condition that would preclude high-volume saline diuresis
• No significant neurologic or psychiatric disorder that would preclude study compliance
• No active uncontrolled infection
• No neuropathy greater than grade 1
• No pre-existing hearing loss greater than grade 1
• No other concurrent serious illness or medical condition that would preclude study participation
• No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent biological response modifiers or immunotherapy
• No concurrent prophylactic colony-stimulating factors (CSFs)

• Concurrent therapeutic CSFs allowed

Chemotherapy:

• No prior chemotherapy for ovarian cancer
• No other concurrent cytotoxic agents

Endocrine therapy:

• No concurrent anticancer hormonal therapy

Radiotherapy:

• No prior radiotherapy for ovarian cancer

Surgery:

• No more than 6 weeks since prior planned pre-chemotherapy surgery for ovarian cancer
• Planned interval debulking allowed
• Concurrent second-look surgery allowed

Other:

• No prior non-surgical therapy for ovarian cancer
• No other concurrent investigational drug therapy
• No other concurrent anticancer treatment
• Concurrent enrollment on CAN-NCIC-OV13/EORTC 55971 allowed

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: collaborator

Grupo Español de Investigación en Cáncer de Ovario

OTHER

Sponsor Role: collaborator

NCIC Clinical Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul J. Hoskins, MD

Role: STUDY_CHAIR

British Columbia Cancer Agency

Ignace B. Vergote, MD, PhD

Role: STUDY_CHAIR

University Hospital, Gasthuisberg

Locations

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Cross Cancer Institute

Edmonton, Alberta, Canada

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, Canada

Lions Gate Hospital

North Vancouver, British Columbia, Canada

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, Canada

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada

The Moncton Hospital

Moncton, New Brunswick, Canada

Atlantic Health Sciences Corporation

Saint John, New Brunswick, Canada

Dr. H. Bliss Murphy Cancer Centre

St. John's, Newfoundland and Labrador, Canada

QEII Health Sciences Center

Halifax, Nova Scotia, Canada

Northeast Cancer Center Health Sciences

Greater Sudbury, Ontario, Canada

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, Canada

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, Canada

Grand River Regional Cancer Centre

Kitchener, Ontario, Canada

London Regional Cancer Program

London, Ontario, Canada

Ottawa Health Research Institute - General Division

Ottawa, Ontario, Canada

Niagara Health System

St. Catharines, Ontario, Canada

Thunder Bay Regional Health Science Centre

Thunder Bay, Ontario, Canada

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada

Windsor Regional Cancer Centre

Windsor, Ontario, Canada

PEI Cancer Treatment Centre,Queen Elizabeth Hospital

Charlottetown, Prince Edward Island, Canada

CHUM - Hopital Notre-Dame

Montreal, Quebec, Canada

Hopital du Sacre-Coeur de Montreal

Montreal, Quebec, Canada

CHUQ-Pavillon Hotel-Dieu de Quebec

Québec, Quebec, Canada

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada

Countries

Canada

References

Hoskins PJ, Vergote I, Stuart G, et al.: A phase III trial of cisplatin plus topotecan followed by paclitaxel plus carboplatin versus standard carboplatin plus paclitaxel as first-line chemotherapy in women with newly diagnosed advanced epithelial ovarian cancer (EOC) (OV.16). A Gynecologic Cancer Intergroup Study of the NCIC CTG, EORTC GCG, and GEICO. [Abstract] J Clin Oncol 26 (Suppl 15): A-LBA5505, 2008.

Reference Type: RESULT

Other Identifiers

CAN-NCIC-OV16

Identifier Type: OTHER

Identifier Source: secondary_id

EORTC-55012

Identifier Type: OTHER

Identifier Source: secondary_id

GEICO-0101

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000069129

Identifier Type: OTHER

Identifier Source: secondary_id

OV16

Identifier Type: -

Identifier Source: org_study_id