Chemotherapy Followed By Surgery Vs Radiotherapy Plus Chemotherapy in Patients With Stage IB or II Cervical Cancer

European Organisation for Research and Treatment of Cancer (EORTC)

Status and phase: Unknown; Phase 3

Conditions: Cervical Cancer

Treatments: Radiation: brachytherapy; Radiation: radiation therapy; Drug: cisplatin; Procedure: neoadjuvant chemotherapy; Procedure: conventional surgery

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT00039338

EORTC-55994

2008-003396-52 (EudraCT Number)

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. Giving chemotherapy drugs before surgery may shrink the tumor so that it can be removed during surgery. Radiation therapy uses high-energy x-rays to kill tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. It is not yet known whether chemotherapy is more effective followed by surgery or combined with radiation therapy in treating cervical cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy followed by radical hysterectomy with that of chemotherapy plus radiation therapy in treating patients who have stage IB or stage II cervical cancer.

Full description

OBJECTIVES:

• Compare the overall and progression-free survival of patients with stage IB2, IIA, or IIB cervical cancer treated with neoadjuvant cisplatin-based chemotherapy followed by radical hysterectomy vs standard therapy comprising concurrent radiotherapy and cisplatin-based chemotherapy.
• Compare the toxicity of these regimens in these patients.
• 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, FIGO stage, age (18 to 50 vs 51 to 75), and histological subtype (adenomatous vs non-adenomatous component). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive neoadjuvant cisplatin-based chemotherapy on day 1. Treatment repeats every 21 days. Within 6 weeks after the last chemotherapy course, patients undergo a type III-V Piver-Rutledge radical hysterectomy. Patients with positive lymph nodes or tumor invasion into the parametria or less than 5 mm from the resection borders after surgery receive standard adjuvant external beam radiotherapy once daily, 5 days a week, for 5-5.6 weeks (25-28 treatment days) followed by external boost radiotherapy or brachytherapy for 1 or 2 days.
• Arm II: Patients receive standard therapy comprising radiotherapy as in arm I concurrently with cisplatin-based chemotherapy once weekly for 6 weeks. Adjuvant hysterectomy is allowed, but not recommended, in case of histologically proven residual tumor.

Treatment in both arms continues in the absence of disease progression or unacceptable toxicity. For patients in both arms, cisplatin may be combined with other chemotherapeutics as long as the minimum platinum dose is given.

Quality of life is assessed at baseline and at 6, 12, 18, and 24 months.

Patients are followed every 3 months for 1 year, every 6 months for 4 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 686 patients (343 per treatment arm) will be accrued for this study within 3.8 years.

Enrollment: 686 estimated patients

Sex: Female

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed cervical cancer, including the following subtypes:

  • Squamous cell carcinoma
  • Adenosquamous cell carcinoma
  • Adenocarcinoma (excluding small cell, clear cell, and other rare variants of the classical adenocarcinoma)

• FIGO stage IB2, IIA (greater than 4 cm), or IIB

PATIENT CHARACTERISTICS:

Age:

• 18 to 75

Performance status:

• WHO 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin less than 1.46 mg/dL

Renal:

• Creatinine clearance greater than 60 mL/min

Other:

• No other prior or concurrent malignancy except adequately treated basal cell skin cancer
• No psychological, familial, sociological, or geographical condition that would preclude study
• Not pregnant

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• Not specified

Other:

• No other concurrent anticancer agent

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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686 participants in 2 patient groups

Chemotherapy followed by surgery

Experimental group

Description:

neoadjuvant chemotherapy (Cisplatin) followed by surgery (radial hysterectomy)

Treatment:

Procedure: neoadjuvant chemotherapy

Procedure: conventional surgery

Drug: cisplatin

Radio-chemotherapy

Active Comparator group

Description:

Concomitant radiotherapy (external radiotherapy combined with external boost or brachytherapy) and chemotherapy (cisplatin)

Treatment:

Procedure: neoadjuvant chemotherapy

Drug: cisplatin

Radiation: brachytherapy

Radiation: radiation therapy