Comparison of Four Combination Chemotherapy Regimens Using Cisplatin in Treating Patients With Stage IVB, Recurrent, or Persistent Cancer of the Cervix

Gynecologic Oncology Group (GOG)

Status and phase: Completed; Phase 3

Conditions: Cervical Adenosquamous Carcinoma; Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma; Recurrent Cervical Carcinoma; Stage IVB Cervical Cancer

Treatments: Drug: Topotecan Hydrochloride; Drug: Cisplatin; Other: Quality-of-Life Assessment; Drug: Vinorelbine Tartrate; Drug: Paclitaxel; Drug: Gemcitabine Hydrochloride

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00064077

U10CA027469 (U.S. NIH Grant/Contract)

GOG-0204 (Other Identifier)

CDR0000306463

NCI-2012-02540 (Registry Identifier)

Details and patient eligibility

About

This randomized phase III trial is studying four combination chemotherapy regimens using cisplatin to compare how well they work in treating women with stage IVB, recurrent, or persistent cancer of the cervix. Drugs used in chemotherapy such as cisplatin, paclitaxel, vinorelbine, gemcitabine, and topotecan, use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which combination chemotherapy regimen containing cisplatin is most effective in treating cervical cancer.

Full description

PRIMARY OBJECTIVES:

I. Compare the survival and response of patients with stage IVB, recurrent, or persistent carcinoma of the cervix when treated with paclitaxel and cisplatin vs vinorelbine and cisplatin vs gemcitabine and cisplatin vs topotecan and cisplatin.

II. Compare the toxic effects of these regimens in these patients. III. Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 4 treatment arms.

ARM I: Patients receive paclitaxel IV over 24 hours on day 1 and cisplatin IV over 1-4 hours on day 2.

ARM II: Patients receive vinorelbine IV over 6-10 minutes on days 1 and 8 and cisplatin IV over 1-4 hours on day 1.

ARM III: Patients receive gemcitabine IV over 30-60 minutes on days 1 and 8 and cisplatin as in arm II.

ARM IV: Patients receive topotecan IV over 30 minutes on days 1-3 and cisplatin as in arm II.

In all arms, treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, before courses 2 and 5, and at 9 months after study entry.

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

Enrollment: 513 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Histologically confirmed squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix

  • Stage IVB, recurrent, or persistent disease

• Not amenable to curative surgery and/or radiotherapy

• At least 1 unidimensionally measurable lesion

  • At least 20 mm by palpation, plain x-ray, CT scan, or MRI OR at least 10 mm by spiral CT scan
  • Biopsy confirmation required if lesion is less than 30 mm
  • Target lesion must be outside of a previously irradiated field

• No craniospinal metastases

• Performance status - GOG 0-1

• Absolute neutrophil count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

• Bilirubin no greater than 1.5 times normal

• Alkaline phosphatase no greater than 3 times normal

• AST no greater than 3 times normal

• Creatinine ≤ 1.2 mg/dL

• Creatinine > 1.2 mg/dL but < 1.5 mg/dL AND creatinine clearance ≥ 50 mL/min

• No bilateral hydronephrosis not alleviated by ureteral stents or percutaneous drainage

• Not pregnant or nursing

• Fertile patients must use effective contraception

• No prior or concurrent malignancy within the past 5 years except nonmelanoma skin cancer

• No prior malignancy whose treatment contraindicates the current study therapy

• No concurrent clinically significant infection

• No concurrent cytokines

• At least 6 weeks since prior chemoradiotherapy and recovered

• No prior chemotherapy (except when concurrently administered with radiotherapy)

• At least 3 weeks since prior radiotherapy and recovered

• Recovered from prior surgery

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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513 participants in 4 patient groups

Arm I (paclitaxel, cisplatin)

Experimental group

Description:

Patients receive paclitaxel IV over 24 hours on day 1 and cisplatin IV over 1-4 hours on day 2.

Treatment:

Drug: Paclitaxel

Other: Quality-of-Life Assessment

Drug: Cisplatin

Arm II (vinorelbine, cisplatin)

Experimental group

Description:

Patients receive vinorelbine IV over 6-10 minutes on days 1 and 8 and cisplatin IV over 1-4 hours on day 1.

Treatment:

Drug: Vinorelbine Tartrate

Other: Quality-of-Life Assessment

Drug: Cisplatin

Arm III (gemcitabine, cisplatin)

Experimental group

Description:

Patients receive gemcitabine IV over 30-60 minutes on days 1 and 8 and cisplatin as in arm II.

Treatment:

Drug: Gemcitabine Hydrochloride

Other: Quality-of-Life Assessment

Drug: Cisplatin

Arm IV (topotecan, cisplatin)

Experimental group

Description:

Patients receive topotecan IV over 30 minutes on days 1-3 and cisplatin as in arm II.

Treatment:

Other: Quality-of-Life Assessment

Drug: Cisplatin

Drug: Topotecan Hydrochloride