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

Brief Title

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

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.

Study Phase

Phase 3

Study Type

Interventional

Primary Outcome

Progression free survival

Secondary Outcome

 Overall Survival

Condition

Fallopian Tube Cancer

Intervention

carboplatin

Study Arms / Comparison Groups

 Cisplatin, Topotecan, Paclitaxel plus Carboplatin

Description:  Arm 1

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Estimated Enrollment

Start Date

August 31, 2001

Completion Date

January 10, 2013

Primary Completion Date

March 5, 2008

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

Gender

Female

Ages

18 Years - 75 Years

Accepts Healthy Volunteers

No

Contacts

Paul J. Hoskins, MD, ,

Location Countries

Canada

Location Countries

Canada

Administrative Informations

NCT ID

NCT00028743

Organization ID

OV16

Secondary IDs

CAN-NCIC-OV16

Responsible Party

Sponsor

Study Sponsor

NCIC Clinical Trials Group

Collaborators

 European Organisation for Research and Treatment of Cancer - EORTC

Study Sponsor

Paul J. Hoskins, MD, Study Chair, British Columbia Cancer Agency

Verification Date

March 2020