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

Sponsor

NCIC Clinical Trials Group (Other)

Overall Status

Completed

CT.gov ID

NCT00028743

Collaborator

European Organisation for Research and Treatment of Cancer - EORTC (Other), Grupo Español de Investigación en Cáncer de Ovario (Other)

819

Enrollment

Locations

Arms

136.3

Actual Duration (Months)

29.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Fallopian Tube Cancer Ovarian Cancer Peritoneal Cavity Cancer	Drug: carboplatin Drug: cisplatin Drug: paclitaxel Drug: topotecan hydrochloride	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

819 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 31, 2001

Actual Primary Completion Date :

Mar 5, 2008

Actual Study Completion Date :

Jan 10, 2013

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Progression free survival [Mar 2008]

Secondary Outcome Measures

Overall Survival [Dec 2012]
Response Rates [March 2008]
Toxic Effects [March 2008]
Quality of Life [March 2008]
CA125 Normalization Rates [March 2008]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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