Radiation Therapy and Capecitabine With or Without Oxaliplatin in Treating Patients Who Are Undergoing Surgery for Stage II or Stage III Rectal Cancer

Unicancer

Status and phase: Completed; Phase 3

Conditions: Colorectal Cancer

Treatments: Drug: oxaliplatin; Procedure: conventional surgery; Drug: capecitabine; Procedure: neoadjuvant therapy; Radiation: radiation therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT00227747

FRE-FNCLCC-ACCORD-12/0405

EU-20522

CDR0000445034

Details and patient eligibility

About

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as capecitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving radiation therapy together with combination chemotherapy before surgery may shrink the tumor so it can be removed. It is not yet known whether giving radiation therapy together with capecitabine is more effective with or without oxaliplatin before surgery in treating rectal cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy, capecitabine, and oxaliplatin to see how well they work compared to radiation therapy and capecitabine in treating patients who are undergoing surgery for stage II or stage III rectal cancer.

Full description

OBJECTIVES:

Primary

• Compare the efficacy of neoadjuvant chemoradiotherapy comprising radiotherapy and capecitabine with vs without oxaliplatin followed by total mesorectal excision, in terms of the rate of complete surgical resection, in patients with resectable stage II or III rectal cancer.

Secondary

• Compare overall and disease-free survival of patients treated with these regimens.
• Compare clinical tumor response in patients treated with these regimens.
• Compare acute and late toxicity of these regimens in these patients.
• Determine biological parameters that predict tumor response and treatment-related toxicity in patients treated with these regimens.
• Compare sphincter preservation and function in patients treated with these regimens.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo radiotherapy once daily 5 days a week and receive capecitabine once daily 5 days a week in weeks 1-5.
• Arm II: Patient undergo radiotherapy and receive capecitabine as in arm I. Patients also receive oxaliplatin once weekly in weeks 1-5.

All patients undergo total mesorectal excision 6 weeks after completion of chemoradiotherapy.

PROJECTED ACCRUAL: A total of 590 patients will be accrued for this study.

Enrollment: 598 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the rectum

  • T3-4, N0-2, M0 disease by endorectal ultrasound

    • T2 disease located in the low rectum allowed provided lower pole is ≤ 6 cm from the anal verge

• Tumor must be accessible to digital rectal examination (i.e., tumor located at low- or mid-rectum)

• Resectable disease treatable with chemoradiotherapy

  • No unresectable disease (i.e., T4 disease with high risk for incomplete gross resection [i.e., R2])

PATIENT CHARACTERISTICS:

Age

• 18 to 80

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin > 10 g/dL

Hepatic

• Alkaline phosphatase normal
• Bilirubin normal

Renal

• Creatinine ≤ 130 μmol/L
• No severe renal insufficiency

Cardiovascular

• No cardiac insufficiency
• No symptomatic coronary artery disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No contraindication to study treatment
• Prior acute intestinal obstruction allowed provided patient underwent surgical diversion with stoma
• No history of other cancer except basal cell skin cancer or carcinoma in situ of the cervix
• No peripheral neuropathy
• No uncontrolled diabetes
• No other uncontrolled severe disease
• No geographical, social, or psychological condition that would preclude study follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for cancer
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for cancer

Surgery

• Not specified

Other

• No concurrent phenytoin
• No concurrent participation in another clinical trial of an experimental medical treatment

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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598 participants in 2 patient groups

Radiothérapie + Xelox

Experimental group

Treatment:

Drug: oxaliplatin

Procedure: conventional surgery

Procedure: neoadjuvant therapy

Radiation: radiation therapy

Drug: capecitabine

Radiothérapie + Capécitabine

Active Comparator group

Treatment:

Procedure: conventional surgery

Procedure: neoadjuvant therapy

Radiation: radiation therapy

Drug: capecitabine