Carboplatin/Paclitaxel +/-Gemcitabine in Treating Patients With Ovarian Epithelial or Fallopian Tube Cancer (AGO-OVAR9)

AGO Study Group

Status and phase: Completed; Phase 3

Conditions: Fallopian Tube Cancer; Ovarian Cancer

Treatments: Drug: TC; Drug: TCG

Study type: Interventional

Funder types: Other

Identifiers

NCT00052468

AGO-OVAR9

EU-20241

CDR0000258429

NORDIC-AGO-OVAR-9

GERCOR-AGO-OVAR-9

Details and patient eligibility

About

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 may kill more tumor cells. It is not yet known whether carboplatin and paclitaxel combined with gemcitabine is more effective than carboplatin and paclitaxel alone in treating ovarian epithelial or fallopian tube cancer.

PURPOSE: This randomized phase III trial is studying carboplatin and paclitaxel combined with gemcitabine to see how well it works compared to paclitaxel and carboplatin alone in treating patients who have undergone surgery for ovarian epithelial or fallopian tube cancer.

Full description

OBJECTIVES:

• Compare overall survival in patients with stage I-IV ovarian epithelial or fallopian tube cancer treated with adjuvant carboplatin and paclitaxel with or without gemcitabine.
• Compare response rates, progression-free survival, and duration of response in patients treated with these regimens.
• Compare toxic effects of these regimens in these patients.
• Compare quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, controlled, multicenter study. Patients are stratified according to FIGO stage (I-IIA vs IIB-IIIC and tumor no greater than 10 mm vs IIB-IIIC and tumor greater than 10 mm or IV), plan for interval surgical debulking (yes vs no), and participating center. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive carboplatin IV over 30-60 minutes and paclitaxel IV over 3 hours on day 1 and gemcitabine IV over 30-60 minutes on days 1 and 8.
• Arm II: Patients receive carboplatin and paclitaxel as in arm I. Treatment in both arms repeats every 21 days for 6 to 10 courses in the absence of disease progression or unacceptable toxicity.

Some patients undergo interval debulking surgery.

Quality of life is assessed at baseline, after courses 3 and 6, and then at 3, 6, and 12 months after completion of study.

Patients are followed every 3 months for 2 years, every 6 months for up to 5 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,716 patients (858 per treatment arm) will be accrued for this study within 2 years.

Enrollment: 1,742 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of one of the following:

  • Ovarian epithelial cancer

    • FIGO stage IA/B G3, IC-IV

  • Fallopian tube cancer

  • Extra-ovarian papillary serous tumor

• The following are ineligible:

  • Low malignant-potential ovarian tumors (borderline tumors)
  • Non-epithelial ovarian tumors
  • Mixed Mullerian tumors

• Must have had definitive surgery within the past 6 weeks

• No symptomatic brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 6 months

Hematopoietic

• WBC at least 3,000/mm^3 OR
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin greater than 10 mg/dL

Hepatic

• Bilirubin no greater than 2 times upper limit of normal

Renal

• Glomerular filtration rate at least 50 mL/min

Cardiovascular

• No congestive heart failure
• No myocardial infarction within the past 6 months
• No New York Heart Association class III or IV heart disease
• No prior atrial or ventricular arrhythmias

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No prior seizures or central nervous system disorder

• No prior severe hypersensitivity reaction to products containing Cremophor EL (e.g., cyclosporine or vitamin K)

• No known hypersensitivity to compounds chemically related to carboplatin, gemcitabine, or paclitaxel

• No preexisting motor or sensory neuropathy greater than grade 1

• No other malignancy within the past 5 years except:

  • Malignancies cured by surgery alone
  • Carcinoma in situ of the cervix
  • Adequately treated basal cell skin cancer

• No complete bowel obstruction

• No other concurrent severe medical condition that would preclude study participation

• No dementia or significantly altered mental status that would preclude study participation

• No concurrent severe active infection

• Geographically accessible for treatment and follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent immunotherapy

Chemotherapy

• No prior chemotherapy
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent hormonal therapy except:

  • Hormone replacement therapy
  • Antiemetic steroids

Radiotherapy

• No prior radiotherapy
• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• Recovered from prior surgery

Other

• No other concurrent antineoplastic agents
• No other concurrent investigational drugs
• No other concurrent clinical trial enrollment

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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1,742 participants in 2 patient groups

TCG

Experimental group

Description:

Paclitaxel 175 mg/m2 day 1, Carboplatin AUC 5 day 1, Gemcitabine 800 mg/m2 day 1 + 8, q 21 days / 6 - 10 courses

Treatment:

Drug: TCG

TC

Active Comparator group

Description:

Paclitaxel 175 mg/m2 day 1, Carboplatin AUC 5 day 1, q 21 days / 6 - 10 courses

Treatment:

Drug: TC