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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2010 by Royal Marsden NHS Foundation Trust.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Royal Marsden NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT00383695
First received: September 29, 2006
Last updated: January 12, 2010
Last verified: January 2010
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Biological: cetuximab
Drug: capecitabine
Drug: oxaliplatin
Procedure: adjuvant therapy
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicentre Randomised Phase II Clinical Trial Comparing Oxaliplatin (Eloxatin), Capecitabine (Xeloda) and Pre-Operative Radiotherapy With or Without Cetuximab Followed by Total Mesorectal Excision for the Treatment of Patients With Magnetic Resonance Imaging (MRI) Defined High Risk Rectal Cancer

Resource links provided by NLM:


Further study details as provided by Royal Marsden NHS Foundation Trust:

Primary Outcome Measures:
  • Pathological complete response rate at time of total mesorectal excision (TME) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Radiological response rates after completion of neoadjuvant therapy [ Designated as safety issue: No ]
  • Complete resection rate (R0 resection) with microscopic clear resection margin (tumor observed > 1 mm from the resection margin), especially circumferential resection margin [ Designated as safety issue: No ]
  • Perioperative measures, including operation time, duration of in-patient stay, perioperative transfusion requirement, and mortality, within 30 days of TME [ Designated as safety issue: No ]
  • Postoperative complications, including wound infection, wound dehiscence, and fistula formation [ Designated as safety issue: No ]
  • Quality of TME as assessed by audit of photographed surgical specimens [ Designated as safety issue: No ]
  • Rate of abdominoperitoneal excision [ Designated as safety issue: No ]
  • Rate of permanent defunctioning colostomies [ Designated as safety issue: No ]
  • Clinical and radiological anastomotic leak rate [ Designated as safety issue: No ]
  • Progression-free survival and patterns of failure [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Safety [ Designated as safety issue: Yes ]
  • Quality of life, including long-term bowel function [ Designated as safety issue: No ]

Estimated Enrollment: 164
Study Start Date: September 2005
Detailed Description:

OBJECTIVES:

  • Compare the pathological complete response rate at total mesorectal excision in patients with high-risk rectal cancer treated with neoadjuvant therapy comprising oxaliplatin, capecitabine, and radiotherapy with or without cetuximab.

OUTLINE: This is a multicenter, open-label, randomized, controlled study. Patients are stratified according to participating center and presence of T4 disease (yes vs no). Patients are randomized to 1 of 2 treatment arms.

  • Arm I:

    • Neoadjuvant chemotherapy: Patients receive oxaliplatin IV over 2 hours on days 1, 22, 43, and 64 and oral capecitabine twice daily on days 1-14, 22-35, 43-56, and 64-77.
    • Neoadjuvant chemoradiotherapy: Patients undergo radiotherapy once daily on days 85-89, 92-96, 99-103, 106-110, 113-117, and 120-124 and receive oral capecitabine twice daily on days 85-126.
    • Surgery: Four to six weeks after completion of chemoradiotherapy, patients undergo total mesorectal excision (TME).
    • Adjuvant therapy: Beginning 6-8 weeks after surgery, patients receive oxaliplatin IV over 2 hours on days 1, 22, 43, and 64 and oral capecitabine twice daily on days 1-14, 22-35, 43-56, and 64-77.
  • Arm II:

    • Neoadjuvant therapy: Patients receive oxaliplatin and capecitabine as in arm I neoadjuvant chemotherapy and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.
    • Neoadjuvant chemoradiotherapy: Patients undergo radiotherapy and receive capecitabine as in arm I neoadjuvant chemoradiotherapy and cetuximab IV over 1 hour on days 85, 92, 99, 106, 113, and 120.
    • Surgery: Four to six weeks after completion of chemoradiotherapy patients undergo TME as in arm I.
    • Adjuvant therapy: Beginning 6-8 weeks after surgery, patients receive oxaliplatin and capecitabine as in arm I adjuvant chemotherapy and cetuximab IV over 1 hour on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed periodically.

After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually for 2 years.

PROJECTED ACCRUAL: A total of 164 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00383695

Locations
Spain
Vall d'Hebron University Hospital
Barcelona, Spain, 08035
Hospital Universitario La Paz
Madrid, Spain, 28046
Hospital Clinico Universitario de Valencia
Valencia, Spain, 46010
Sweden
Karolinska University Hospital - Solna
Stockholm, Sweden, S-171 76
Uppsala University Hospital
Uppsala, Sweden, S-75185
United Kingdom
Royal Bournemouth Hospital NHS Trust
Bournemouth, England, United Kingdom, BH7 7DW
Sussex Cancer Centre at Royal Sussex County Hospital
Brighton, England, United Kingdom, BN2 5BE
Eastbourne District General Hospital
Eastbourne, England, United Kingdom, BN21 2UD
Cancer Research UK Clinical Groups at Guy's King's & St. Thomas' Hospitals
London, England, United Kingdom, SE5 9NU
Mid Kent Oncology Centre at Maidstone Hospital
Maidstone, England, United Kingdom, ME16 9QQ
Dorset Cancer Centre
Poole Dorset, England, United Kingdom, BH15 2JB
Southampton General Hospital
Southampton, England, United Kingdom, SO16 6YD
Royal Marsden - Surrey
Sutton, England, United Kingdom, SM2 5PT
Sponsors and Collaborators
Royal Marsden NHS Foundation Trust
Investigators
Study Chair: David Cunningham, MD Royal Marsden NHS Foundation Trust
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00383695     History of Changes
Other Study ID Numbers: CDR0000503948, RMNHS-RMH-CCR-2553, EU-20635, EUDRACT-2004-004707-38, CRUK-EXPERT-C, MERCK-RMNHS-RMH-CCR-2553
Study First Received: September 29, 2006
Last Updated: January 12, 2010
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Royal Marsden NHS Foundation Trust:
adenocarcinoma of the rectum
stage I rectal cancer
stage II rectal cancer
stage III rectal cancer

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases
Oxaliplatin
Capecitabine
Cetuximab
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 16, 2014