Clinical trial NCT00028743: Combination Chemotherapy Regimens in Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Fallopian Tube Cancer
Ovarian Cancer
Peritoneal Cavity Cancer
Keywords: stage II ovarian epithelial cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
fallopian tube cancer
peritoneal cavity cancer
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: European Organisation for Research and Treatment of Cancer - EORTC
name: Grupo Español de Investigación en Cáncer de Ovario
First posted: 2003-01-27
Enrollment: 819
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Progression free survival
timeFrame: Mar 2008
Secondary outcomes:
measure: Overall Survival
timeFrame: Dec 2012
measure: Response Rates
timeFrame: March 2008
measure: Toxic Effects
timeFrame: March 2008
measure: Quality of Life
timeFrame: March 2008
measure: CA125 Normalization Rates
timeFrame: March 2008
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Kelowna
country: Canada
facility: BCCA - Cancer Centre for the Southern Interior
state: British Columbia
city: North Vancouver
country: Canada
facility: Lions Gate Hospital
state: British Columbia
city: Surrey
country: Canada
facility: BCCA - Fraser Valley Cancer Centre
state: British Columbia
city: Vancouver
country: Canada
facility: BCCA - Vancouver Cancer Centre
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Moncton
country: Canada
facility: The Moncton Hospital
state: New Brunswick
city: Saint John
country: Canada
facility: Atlantic Health Sciences Corporation
state: New Brunswick
city: St. John's
country: Canada
facility: Dr. H. Bliss Murphy Cancer Centre
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: QEII Health Sciences Center
state: Nova Scotia
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre at Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston
state: Ontario
city: Kitchener
country: Canada
facility: Grand River Regional Cancer Centre
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Health Research Institute - General Division
state: Ontario
city: St. Catharines
country: Canada
facility: Niagara Health System
state: Ontario
city: Sudbury
country: Canada
facility: Northeast Cancer Center Health Sciences
state: Ontario
city: Thunder Bay
country: Canada
facility: Thunder Bay Regional Health Science Centre
state: Ontario
city: Toronto
country: Canada
facility: Univ. Health Network-Princess Margaret Hospital
state: Ontario
city: Windsor
country: Canada
facility: Windsor Regional Cancer Centre
state: Ontario
city: Charlottetown
country: Canada
facility: PEI Cancer Treatment Centre,Queen Elizabeth Hospital
state: Prince Edward Island
city: Montreal
country: Canada
facility: CHUM - Hopital Notre-Dame
state: Quebec
city: Montreal
country: Canada
facility: Hopital du Sacre-Coeur de Montreal
state: Quebec
city: Quebec City
country: Canada
facility: CHUQ-Pavillon Hotel-Dieu de Quebec
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre hospitalier universitaire de Sherbrooke
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
Study officials:
affiliation: British Columbia Cancer Agency
name: Paul J. Hoskins, MD
role: STUDY_CHAIR
affiliation: University Hospital, Gasthuisberg
name: Ignace B. Vergote, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.