Radiation Therapy, Irinotecan, and Cetuximab in Treating Patients Who Are Undergoing Surgery for Stage III or Stage IV Rectal Cancer - Full Text View

Sponsored by:	Centre Hospitalier Universitaire Vaudois
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00392470

Purpose

RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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 radiation therapy together with irinotecan and cetuximab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase I trial is studying the side effects and best dose of irinotecan when given together with cetuximab and radiation therapy in treating patients who are undergoing surgery for stage III or stage IV rectal cancer.

Condition	Intervention	Phase
Colorectal Cancer	Drug: cetuximab Drug: irinotecan hydrochloride Procedure: 3-dimensional conformal radiation therapy Procedure: conventional surgery Procedure: intensity-modulated radiation therapy Procedure: neoadjuvant therapy	Phase I

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Irinotecan Irinotecan hydrochloride Cetuximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Neoadjuvant Conformal Radiotherapy and Concomitant CPT-11 and EGFR Inhibition With Cetuximab in Patients With Rectal Cancer Phase I Study

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

Primary Outcome Measures:

Radiological (clinical) tumor response before surgery [ Designated as safety issue: No ]
Pathologic response rate and histological degree of tumor regression as measured by Mandard TRG score [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	August 2006

Detailed Description:

OBJECTIVES:

Primary

Determine the toxicity of irinotecan hydrochloride and cetuximab in patients with stage III or IV rectal cancer undergoing conformal or intensity-modulated radiotherapy.

Secondary

Determine the rate of pathologic response and histological degree of tumor regression in patients treated with this regimen.
Determine the complete resection rate (R0) in patients treated with this regimen.
Determine the sphincter preservation rate in patients treated with this regimen.
Determine the 30-day postoperative complication rate in patients treated with this regimen.
Determine the local and distant relapse rate and site of disease failure in patients treated with this regimen.
Estimate the predictive value of fludeoxyglucose F 18 positron emission tomography/CT scan for treatment response compared to endoscopic ultrasonography (EUS), CT scan, and MRI in patients treated with this regimen.
Determine the late toxicity of this regimen in these patients.
Determine the clinical (radiological) tumor response (i.e., MRI, CT scan, EUS) in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of irinotecan hydrochloride.

Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, and 43 followed by irinotecan hydrochloride IV over 30 minutes on days 1, 8, 15, 22, and 29. Patients also undergo conformal radiotherapy or intensity-modulated radiotherapy on days 1-5 for 5 weeks. Patients undergo radical surgery 3-4 weeks after completion of neoadjuvant therapy.

Cohorts of 3-6 patients receive escalating doses of irinotecan hydrochloride until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

After completion of study treatment, patients are followed periodically for at least 5 years.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years to 74 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the rectum
- T3-4 and/or N+ (stage IIIB, IIIC, or IV disease)
Liver or lung metastasis allowed
No recurrent disease

PATIENT CHARACTERISTICS:

WHO performance status 0 or 1
Hematologic, liver, and renal function normal
Considered fit for chemotherapy, radiotherapy, and surgery
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after completion of study treatment
No symptomatic heart disease or myocardial infarction during the past 6 months
No chronic inflammatory bowel disease
No malignant tumor during the past 5 years except for completely surgically resected carcinoma of the cervix or squamous cell carcinoma of the skin
No other concurrent malignant tumor

PRIOR CONCURRENT THERAPY:

No prior chemotherapy or radiotherapy for rectal cancer
No prior radiotherapy to the pelvis

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00392470

Locations

Switzerland
Centre Hospitalier Universitaire Vaudois	Recruiting
Lausanne, Switzerland, CH-1011
Contact: Michael Montemurro, MD 41-21-314-4530
Institut Ludwig de Recherche sur le Cancer	Recruiting
Epalinges, Switzerland, 1066
Contact: Curzio Ruegg, MD 44-412-1692-5853
Kantonspital Aarau	Recruiting
Aarau, Switzerland, CH-5000
Contact: Peter Moosmann, MD, PhD 41-62-838-6051 peter.moosmann@ksa.ch

Sponsors and Collaborators

Centre Hospitalier Universitaire Vaudois

Investigators

Study Chair:

Michael Montemurro, MD

Centre Hospitalier Universitaire Vaudois

More Information

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

Study ID Numbers:	CDR0000512816, CHUV-CEPO-CORCC-204-5, EU-20645, PFIZER-CHUV-CAPO-CARK-204-5, MERCK-CHUV-CAPO-CARK-204-5
Study First Received:	October 25, 2006
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00392470
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of the rectum
stage III rectal cancer
stage IV rectal cancer

Study placed in the following topic categories:

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

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

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

Therapeutic Uses
Enzyme Inhibitors
Antineoplastic Agents, Phytogenic
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009