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

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

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.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cavity Cancer
• Intervention / Treatment: Drug: carboplatin; Drug: cisplatin; Drug: paclitaxel; Drug: topotecan hydrochloride

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.

• Study Type: Interventional
• Enrollment (Actual): 819
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • BCCA - Cancer Centre for the Southern Interior
    • North Vancouver, British Columbia, Canada, V7L 2L7
      • Lions Gate Hospital
    • Surrey, British Columbia, Canada, V3V 1Z2
      • BCCA - Fraser Valley Cancer Centre
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA - Vancouver Cancer Centre
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • The Moncton Hospital
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Atlantic Health Sciences Corporation
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, AIB 3V6
      • Dr. H. Bliss Murphy Cancer Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • QEII Health Sciences Center
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre at Hamilton Health Sciences
    • Kingston, Ontario, Canada, K7L 5P9
      • Cancer Centre of Southeastern Ontario at Kingston
    • Kitchener, Ontario, Canada, N2G 1G3
      • Grand River Regional Cancer Centre
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Health Research Institute - General Division
    • St. Catharines, Ontario, Canada, L2R 7C6
      • Niagara Health System
    • Sudbury, Ontario, Canada, P3E 5J1
      • Northeast Cancer Center Health Sciences
    • Thunder Bay, Ontario, Canada, P7B 6V4
      • Thunder Bay Regional Health Science Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Univ. Health Network-Princess Margaret Hospital
    • Windsor, Ontario, Canada, N8W 2X3
      • Windsor Regional Cancer Centre
  • Prince Edward Island
    • Charlottetown, Prince Edward Island, Canada, C1A 8T5
      • PEI Cancer Treatment Centre,Queen Elizabeth Hospital
  • Quebec
    • Montreal, Quebec, Canada, H4J 1C5
      • Hôpital du Sacré-Coeur de Montreal
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM - Hopital Notre-Dame
    • Quebec City, Quebec, Canada, G1R 2J6
      • CHUQ-Pavillon Hotel-Dieu de Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Universitaire de Sherbrooke
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cisplatin, Topotecan, Paclitaxel plus Carboplatin; Arm 1	Drug: carboplatin; Arm 1 = 4 cycles vs Arm 2 = 8 cycles AUC5 (30 mins) day 1 of 21 day cycle; Drug: cisplatin; 4 cycles 50mg/m2 (60 mins) day 1 of 21 day cycle; Drug: paclitaxel; Arm 1 = 4 cycles vs Arm 2 = 8 cycles 175mg/m2 (3 hours) day 1 of 21 day cycle; Drug: topotecan hydrochloride; 4 cycles .75mg/m2 (30 mins) days 1-5 of 21 day cycle
Active Comparator: Paclitaxel plus Carboplatin; Arm 2	Drug: carboplatin; Arm 1 = 4 cycles vs Arm 2 = 8 cycles AUC5 (30 mins) day 1 of 21 day cycle; Drug: paclitaxel; Arm 1 = 4 cycles vs Arm 2 = 8 cycles 175mg/m2 (3 hours) day 1 of 21 day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression free survival	Mar 2008

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival	Dec 2012
Response Rates	March 2008
Toxic Effects	March 2008
Quality of Life	March 2008
CA125 Normalization Rates	March 2008

Collaborators and Investigators

• Sponsor: NCIC Clinical Trials Group
• Collaborators: European Organisation for Research and Treatment of Cancer - EORTC; Grupo Español de Investigación en Cáncer de Ovario
• Investigators: Study Chair: Paul J. Hoskins, MD, British Columbia Cancer Agency

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2001
• Primary Completion (Actual): March 5, 2008
• Study Completion (Actual): January 10, 2013

Study Registration Dates

• First Submitted: January 4, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): April 2, 2020
• Last Update Submitted That Met QC Criteria: March 31, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: stage III ovarian epithelial cancer; stage IV ovarian epithelial cancer; fallopian tube cancer; stage II ovarian epithelial cancer; peritoneal cavity cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Ovarian Neoplasms; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Carboplatin; Paclitaxel; Cisplatin; Topotecan
• Other Study ID Numbers: OV16; CAN-NCIC-OV16 (Other Identifier: PDQ); EORTC-55012 (Other Identifier: EORTC); GEICO-0101 (Other Identifier: GEICO); CDR0000069129 (Other Identifier: PDQ)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No