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

Ovarian Cancer Clinical Trial

Official title:

A Phase III Study of Cisplatin Plus Topotecan Followed by Paclitaxel Plus Carboplatin Versus Paclitaxel Plus Carboplatin as First Line Chemotherapy in Women With Newly Diagnosed Advanced Epithelial Ovarian Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00028743
• Other study ID #: OV16
• Secondary ID: CAN-NCIC-OV16EOR
• Status: Completed
• Phase: Phase 3
• Start date: August 31, 2001
• Est. completion date: January 10, 2013

Study information

• Verified date: March 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 819
• Est. completion date: January 10, 2013
• Est. primary completion date: March 5, 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms
• Peritoneal Cavity Cancer

Intervention

Drug:
• carboplatin
Arm 1 = 4 cycles vs Arm 2 = 8 cycles AUC5 (30 mins) day 1 of 21 day cycle
• cisplatin
4 cycles 50mg/m2 (60 mins) day 1 of 21 day cycle
• paclitaxel
Arm 1 = 4 cycles vs Arm 2 = 8 cycles 175mg/m2 (3 hours) day 1 of 21 day cycle
• topotecan hydrochloride
4 cycles .75mg/m2 (30 mins) days 1-5 of 21 day cycle

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	PEI Cancer Treatment Centre,Queen Elizabeth Hospital	Charlottetown	Prince Edward Island
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	QEII Health Sciences Center	Halifax	Nova Scotia
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	BCCA - Cancer Centre for the Southern Interior	Kelowna	British Columbia
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	The Moncton Hospital	Moncton	New Brunswick
Canada	CHUM - Hopital Notre-Dame	Montreal	Quebec
Canada	Hopital du Sacre-Coeur de Montreal	Montreal	Quebec
Canada	Lions Gate Hospital	North Vancouver	British Columbia
Canada	Ottawa Health Research Institute - General Division	Ottawa	Ontario
Canada	CHUQ-Pavillon Hotel-Dieu de Quebec	Quebec City	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Atlantic Health Sciences Corporation	Saint John	New Brunswick
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Centre hospitalier universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	Niagara Health System	St. Catharines	Ontario
Canada	Dr. H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador
Canada	Northeast Cancer Center Health Sciences	Sudbury	Ontario
Canada	BCCA - Fraser Valley Cancer Centre	Surrey	British Columbia
Canada	Thunder Bay Regional Health Science Centre	Thunder Bay	Ontario
Canada	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia
Canada	Windsor Regional Cancer Centre	Windsor	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba

Sponsors (3)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group	European Organisation for Research and Treatment of Cancer - EORTC, Grupo Español de Investigación en Cáncer de Ovario

Country where clinical trial is conducted

Canada, 

References & Publications (1)

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival		Mar 2008
Secondary	Overall Survival		Dec 2012
Secondary	Response Rates		March 2008
Secondary	Toxic Effects		March 2008
Secondary	Quality of Life		March 2008
Secondary	CA125 Normalization Rates		March 2008