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

• ClinicalTrials.gov Identifier: NCT00227747
• Recruitment Status: Completed
• First Posted: September 28, 2005
• Last Update Posted: February 17, 2021
• Sponsor: UNICANCER
• Information provided by (Responsible Party): UNICANCER

Tracking Information

• First Submitted Date: September 26, 2005
• First Posted Date: September 28, 2005
• Last Update Posted Date: February 17, 2021
• Actual Study Start Date: November 8, 2005
• Actual Primary Completion Date: October 22, 2008 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 16, 2007): Rate of complete surgical resection
• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: May 16, 2007)

• Overall survival
• Disease-free survival
• Sphincter preservation
• Sphincter function
• Biological parameters that predict tumor response and treatment-related toxicity
• Acute and late toxicity

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Radiation Therapy and Capecitabine With or Without Oxaliplatin in Treating Patients Who Are Undergoing Surgery for Stage II or Stage III Rectal Cancer
• Official Title: Randomized Phase III Trial Comparing in a Preoperative Schedule the Result of Two Concurrent Chemoradiation Schemes (45 Gy + Capecitabine vs 50 Gy + Capecitabine - Oxaliplatin) on the Rate of Sterilization of the Operative Specimen in Resectable Rectal Carcinomas T3-4 No-2 Mo

Brief Summary

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.

Detailed 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Colorectal Cancer

Intervention

• Drug: capecitabine
• Drug: oxaliplatin
• Procedure: conventional surgery
• Procedure: neoadjuvant therapy
• Radiation: radiation therapy

Study Arms

• Experimental: Radiothérapie + Xelox
  Interventions:

  • Drug: capecitabine
  • Drug: oxaliplatin
  • Procedure: conventional surgery
  • Procedure: neoadjuvant therapy
  • Radiation: radiation therapy
• Active Comparator: Radiothérapie + Capécitabine
  Interventions:

  • Drug: capecitabine
  • Procedure: conventional surgery
  • Procedure: neoadjuvant therapy
  • Radiation: radiation therapy

Publications *

• Gerard JP, Azria D, Gourgou-Bourgade S, Martel-Laffay I, Hennequin C, Etienne PL, Vendrely V, Francois E, de La Roche G, Bouche O, Mirabel X, Denis B, Mineur L, Berdah JF, Mahe MA, Becouarn Y, Dupuis O, Lledo G, Montoto-Grillot C, Conroy T. Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2. J Clin Oncol. 2010 Apr 1;28(10):1638-44. doi: 10.1200/JCO.2009.25.8376. Epub 2010 Mar 1.
• Azria D, Doyen J, Jarlier M, Martel-Lafay I, Hennequin C, Etienne P, Vendrely V, Francois E, de La Roche G, Bouche O, Mirabel X, Denis B, Mineur L, Berdah J, Mahe M, Becouarn Y, Dupuis O, Lledo G, Seitz J, Bedenne L, Gourgou-Bourgade S, Juzyna B, Conroy T, Gerard J. Late toxicities and clinical outcome at 5 years of the ACCORD 12/0405-PRODIGE 02 trial comparing two neoadjuvant chemoradiotherapy regimens for intermediate-risk rectal cancer. Ann Oncol. 2017 Oct 1;28(10):2436-2442. doi: 10.1093/annonc/mdx351.

Recruitment Information

• Recruitment Status: Completed
• Estimated Enrollment (submitted: February 15, 2021): 598
• Original Enrollment: Not Provided
• Actual Study Completion Date: July 15, 2013
• Actual Primary Completion Date: October 22, 2008 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT00227747
• Other Study ID Numbers: CDR0000445034; FRE-FNCLCC-ACCORD-12/0405; EU-20522
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: UNICANCER
• Original Responsible Party: Not Provided
• Current Study Sponsor: UNICANCER
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Jean-Pierre Gerard, MD; Centre Antoine Lacassagne

• PRS Account: UNICANCER
• Verification Date: February 2021