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

Sponsored by:	Royal Marsden - Surrey
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00383695

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	Drug: capecitabine Drug: cetuximab Drug: oxaliplatin Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Procedure: radiation therapy	Phase II

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Capecitabine Oxaliplatin Cetuximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control
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

Further study details as provided by National Cancer Institute (NCI):

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
Hospital Clinico Universitario de Valencia	Recruiting
Valencia, Spain, 46010
Contact: Andres Cervantes, MD, PhD 34-963-862-625 andres.cervantes@uv.es
Hospital Universitario La Paz	Recruiting
Madrid, Spain, 28046
Contact: Jaime Feliu, MD 34-912-071-140
Vall d'Hebron University Hospital	Recruiting
Barcelona, Spain, 08035
Contact: Josep Tabernero, MD 34-93-274-6085 jtabernero@vhebron.net
Sweden
Karolinska University Hospital - Solna	Recruiting
Stockholm, Sweden, S-171 76
Contact: Bengt Glimelius, MD 46-851-773-047
Uppsala University Hospital	Recruiting
Uppsala, Sweden, S-75185
Contact: Bengt Glimelius, MD 46-186-115-513
United Kingdom, England
Cancer Research UK Clinical Groups at Guy's King's & St. Thomas' Hospitals	Recruiting
London, England, United Kingdom, SE5 9NU
Contact: Paul Ross 44-207-188-7188
Sussex Cancer Centre at Royal Sussex County Hospital	Recruiting
Brighton, England, United Kingdom, BN2 5BE
Contact: Andrew Webb, MD 44-12-7369-6955
Mid Kent Oncology Centre at Maidstone Hospital	Recruiting
Maidstone, England, United Kingdom, ME16 9QQ
Contact: Mark Hill, MD 44-162-272-9000
Poole Hospital NHS Trust	Recruiting
Poole Dorset, England, United Kingdom, BH15 2JB
Contact: Tamas Hickish, MD 44-120-266-5511
Royal Bournemouth Hospital NHS Trust	Recruiting
Bournemouth, England, United Kingdom, BH7 7DW
Contact: Tamas Hickish, MD 44-1202-704-789 tamas.hickish@rbch.nhs.uk
Royal Marsden - Surrey	Recruiting
Sutton, England, United Kingdom, SM2 5PT
Contact: Yu J. Chua 44-20-8661-3279
Southampton General Hospital	Recruiting
Southampton, England, United Kingdom, SO16 6YD
Contact: Andrew Bateman, MD 44-23-8079-6184
Eastbourne District General Hospital	Recruiting
Eastbourne, England, United Kingdom, BN21 2UD
Contact: Fiona McKinna, MD 44-132-3411-7400 fiona.mckinna@bsuh.nhs.uk

Sponsors and Collaborators

Royal Marsden - Surrey

Investigators

Study Chair:

David Cunningham, MD

Royal Marsden - Surrey

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

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:	August 13, 2008
ClinicalTrials.gov Identifier:	NCT00383695
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Capecitabine
Digestive System Neoplasms
Rectal Neoplasms
Gastrointestinal Diseases
Cetuximab
Colonic Diseases
Intestinal Diseases
Rectal Diseases

Intestinal Neoplasms
Rectal neoplasm
Oxaliplatin
Digestive System Diseases
Gastrointestinal Neoplasms
Adenocarcinoma
Rectal cancer
Colorectal Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Neoplasms
Antimetabolites, Antineoplastic
Neoplasms by Site

Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009