Oxaliplatin, Capecitabine, and Radiation Therapy With or Without Cetuximab in Treating Patients Undergoing Surgery for High-Risk Rectal Cancer

NCT00383695 | Unknown Phase 2 DMC

• 6 other identifiers: CDR0000503948RMNHS-RMH-CCR-2553EU-20635EUDRACT-2004-004707-38CRUK-EXPERT-CMERCK-RMNHS-RMH-CCR-2553
• Study Type: interventional
• Target: 164
• Locations: 3 countries
• Sites: 13

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and capecitabine, 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. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving chemotherapy and radiation therapy with or without cetuximab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether giving oxaliplatin, capecitabine, and radiation therapy is more effective with or without cetuximab when given before surgery in treating rectal cancer. PURPOSE: This randomized phase II trial is studying oxaliplatin, capecitabine, and radiation therapy to compare how well they work with or without cetuximab in treating patients undergoing surgery for high-risk rectal cancer.

Conditions

Colorectal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Pathological complete response rate at time of total mesorectal excision (TME)

Secondary Outcomes (12)

• Radiological response rates after completion of neoadjuvant therapy

• Complete resection rate (R0 resection) with microscopic clear resection margin (tumor observed > 1 mm from the resection margin), especially circumferential resection margin

• Perioperative measures, including operation time, duration of in-patient stay, perioperative transfusion requirement, and mortality, within 30 days of TME

• Postoperative complications, including wound infection, wound dehiscence, and fistula formation

• Quality of TME as assessed by audit of photographed surgical specimens

Interventions

cetuximab BIOLOGICAL

capecitabine DRUG

oxaliplatin DRUG

adjuvant therapy PROCEDURE

conventional surgery PROCEDURE

neoadjuvant therapy PROCEDURE

radiation therapy RADIATION

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed adenocarcinoma or undifferentiated non-small cell carcinoma of the rectum * MRI-defined high-risk, operable disease, defined by ≥ 1 of the following: * Tumors within 1 mm of mesorectal fascia (i.e., circumferential resection margin threatened or involved) * T3 tumors at or below levators * Tumors extending ≥ 5 mm into perirectal fat * T4 tumors * Presence of extramural venous invasion (primary tumor is therefore at least T3) * No evidence of metastatic disease by CT scan of the chest and abdomen or, if required, by positron emission tomography scan or biopsy * No rectal cancer that is unlikely to be operable even after neoadjuvant treatment (i.e., tumor involving the internal iliac vessels) * No T1-2 rectal cancer, in the absence of other high-risk factors * T2 tumors within 1 mm of mesorectal fascia allowed * No recurrent disease PATIENT CHARACTERISTICS: * WHO performance status 0-2 * Life expectancy \> 3 months * WBC \> 3,000/mm³ * Absolute neutrophil count \> 1,500/mm³ * Platelet count \> 100,000/mm³ * Bilirubin \< 1.5 times upper limit of normal (ULN) * Transaminases \< 2.5 times ULN * Creatinine normal OR creatinine clearance \> 50 mL/min * Not pregnant or nursing * Fertile patients must use effective contraception * No concurrent uncontrolled medical condition * No other active malignant disease within the past 10 years except nonmelanoma skin cancer or carcinoma in situ of the cervix * No contraindications to MRI (e.g., pacemaker) * No medical or psychiatric conditions that would preclude informed consent * No known malabsorption syndrome or lack of physical integrity of the upper gastrointestinal tract * No clinically significant (i.e., active) cardiac disease, including any of the following: * Congestive heart failure * Symptomatic coronary artery disease * Cardiac dysrhythmia (e.g., atrial fibrillation, even if controlled with medication) * Myocardial infarction within the past 12 months * No symptoms or history of peripheral neuropathy PRIOR CONCURRENT THERAPY: * No prior chemotherapy, radiotherapy, or investigational treatment for rectal cancer * No other concurrent cytotoxic agents or investigational drugs * No concurrent sorivudine or sorivudine 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

• Royal Marsden NHS Foundation Trust: lead

Study Sites (13)

Vall d'Hebron University Hospital

Barcelona, 08035, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Karolinska University Hospital - Solna

Stockholm, S-171 76, Sweden

Location

Uppsala University Hospital

Uppsala, S-75185, Sweden

Location

Royal Bournemouth Hospital NHS Trust

Bournemouth, England, BH7 7DW, United Kingdom

Location

Sussex Cancer Centre at Royal Sussex County Hospital

Brighton, England, BN2 5BE, United Kingdom

Location

Eastbourne District General Hospital

Eastbourne, England, BN21 2UD, United Kingdom

Location

Cancer Research UK Clinical Groups at Guy's King's & St. Thomas' Hospitals

London, England, SE5 9NU, United Kingdom

Location

Mid Kent Oncology Centre at Maidstone Hospital

Maidstone, England, ME16 9QQ, United Kingdom

Location

Dorset Cancer Centre

Poole Dorset, England, BH15 2JB, United Kingdom

Location

Southampton General Hospital

Southampton, England, SO16 6YD, United Kingdom

Location

Royal Marsden - Surrey

Sutton, England, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Rectal Neoplasms

Interventions

Cetuximab; Capecitabine; Oxaliplatin; Chemotherapy, Adjuvant; Neoadjuvant Therapy; Radiotherapy

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; 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; Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• David Cunningham, MD

  Royal Marsden NHS Foundation Trust

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 29, 2006
• First Posted: October 3, 2006
• Study Start: September 1, 2005
• Last Updated: January 13, 2010

Record last verified: 2010-01

Locations

SE (2); GB (8); ES (3)