Chemotherapy and Radiation Therapy Before Surgery Followed by Capecitabine With or Without Oxaliplatin in Treating Patients With Locally Advanced Rectal Cancer

NCT00766155 | Completed Phase 3

• 5 other identifiers: EORTC-40054-22062EU-20880PETACC-6ROCHE-EORTC-400542006-006532-21
• Study Type: interventional
• Target: 1,094
• Locations: 0 countries
• Sites: N/A

Brief Summary

RATIONALE: 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy that uses a 3-dimensional image of the tumor to help focus thin beams of radiation directly on the tumor may kill more tumor cells and have fewer side effects. Giving chemotherapy together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether capecitabine is more effective with or without oxaliplatin in treating patients with rectal cancer. PURPOSE: This randomized phase III trial is studying giving chemotherapy together with radiation therapy before surgery followed by capecitabine with or without oxaliplatin to see how well it works in treating patients with locally advanced rectal cancer.

Conditions

Colorectal Cancer

Keywords

stage II rectal cancer; stage III rectal cancer; adenocarcinoma of the rectum

Outcome Measures

Primary Outcomes (1)

• Disease-free survival

Secondary Outcomes (10)

• Overall survival within at least the first 5 years after treatment

• Loco-regional failure, defined as local or regional recurrence, inoperable disease, or R1 or R2 resection

• Distant failure (i.e., distant metastasis)

• Pathological down-stage (ypT0, 2N0) rate

• Pathological complete remission (ypT0N0) rate

Study Arms (2)

Arm I

ACTIVE COMPARATOR

Patients receive oral capecitabine twice daily and undergo concurrent 3-dimensional conformal radiotherapy 5 days a week on days 1-33. Patients may receive additional chemoradiotherapy on days 36-38. Patients then undergo surgery. Beginning 4-8 weeks after surgery, patients receive capecitabine twice daily on day 1-15. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: capecitabine

Arm II

EXPERIMENTAL

Patients receive oral capecitabine twice daily and undergo concurrent 3-dimensional conformal radiotherapy 5 days a week on days 1-33. Patients also receive oxaliplatin IV over 1 hour on days 1, 8, 15, 22, and 29 prior to radiotherapy followed by surgery. Patients may receive additional chemoradiotherapy on days 36-38. Beginning 4-8 weeks later, patients receive oxaliplatin IV over 2 hours on day 1, and oral capecitabine twice daily on days 1-15. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: capecitabine; Drug: oxaliplatin

Interventions

capecitabine DRUG

Given orally

Arm I; Arm II

oxaliplatin DRUG

Given IV

Arm II

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed adenocarcinoma of the rectum * Tumor ≤ 12 cm from the anal verge * Stage T3-4 or any node-positive disease * No evidence of metastatic disease (confirmed by negative CT scan of the chest and abdomen) * Resectable disease or expected to become resectable after preoperative chemoradiation * May only be randomized once in this trial PATIENT CHARACTERISTICS: * WHO/ECOG performance status 0-2 * Hemoglobin ≥ 10.0 g/dL (transfusion allowed to achieve or maintain levels) * ANC ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * ALT and AST ≤ 2.5 times upper level of normal (ULN) * Alkaline phosphatase ≤ 2.5 times ULN * Total bilirubin ≤ 1.5 times ULN * Creatinine clearance \> 50 mL/min * Creatinine ≤ 1.5 times ULN * Able to swallow tablets * No prior or concurrent malignancies within the past 5 years except for adequately treated cone-biopsied carcinoma in situ of the cervix or basal cell carcinoma of the skin * No clinically significant (i.e., active) cardiac disease, including any of the following: * Congestive heart failure * Symptomatic coronary artery disease * Cardiac arrhythmia * No myocardial infarction within the past 12 months * No known significant impairment of intestinal resorption (e.g., chronic diarrhea, inflammatory bowel disease) * No pre-existing conditions that would preclude chemoradiotherapy or radiotherapy (i.e., fistulas, severe ulcerative colitis \[particularly patients currently taking sulfasalazine\], Crohn's disease, or prior adhesions) * No peripheral neuropathy ≥ grade 2 by CTCAE v3.0 * No serious uncontrolled intercurrent infections or other serious uncontrolled concomitant disease * No history of uncontrolled seizures, central nervous system disorders or psychiatric disability that, in the opinion of the principal investigator, is clinically significant and would preclude giving informed consent or interfere with compliance with oral drug administration * No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule * Not pregnant or nursing * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: * No prior cytotoxic chemotherapy or radiation therapy for rectal cancer * No prior radiation therapy to the pelvis * No prior or concurrent investigational drug, agent, or procedure * More than 4 weeks since prior participation in the active or follow-up period of another investigational protocol * No known allergy or any other adverse reaction to any of the study drugs or to any related compound * No known dihydropyrimidine dehydrogenase deficiency * No organ allograft requiring immunosuppressive therapy * No concurrent sorivudine or chemically related analogues (e.g., brivudine)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Related Publications (1)

• Schmoll HJ, Stein A, Van Cutsem E, Price T, Hofheinz RD, Nordlinger B, Daisne JF, Janssens J, Brenner B, Reinel H, Hollerbach S, Caca K, Fauth F, Hannig CV, Zalcberg J, Tebbutt N, Mauer ME, Marreaud S, Lutz MP, Haustermans K. Pre- and Postoperative Capecitabine Without or With Oxaliplatin in Locally Advanced Rectal Cancer: PETACC 6 Trial by EORTC GITCG and ROG, AIO, AGITG, BGDO, and FFCD. J Clin Oncol. 2021 Jan 1;39(1):17-29. doi: 10.1200/JCO.20.01740. Epub 2020 Oct 1.

  PMID: 33001764 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Rectal Neoplasms

Interventions

Capecitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Study Officials

• Hans-Joachim Schmoll, MD, PhD

  Martin-Luther-Universität Halle-Wittenberg

  STUDY CHAIR

• Karin Haustermans

  U.Z. Gasthuisberg, Leuven

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2008
• First Posted: October 3, 2008
• Study Start: August 1, 2008
• Primary Completion: September 1, 2011
• Last Updated: October 12, 2016

Record last verified: 2016-10