Safety Study of Cetuximab in Combination With Oxaliplatin, Capecitabine, and Radiation Therapy Followed by Surgery for Locally-advanced Rectal Cancer - Full Text View

Purpose

To determine the MTD and DLTs of oxaliplatin and capecitabine when combined with C225 and radiotherapy (Phase I)
To determine the pathologic response rate of C225 in combination with this neoadjuvant cytotoxic regimen (Phase II)

Condition	Intervention	Phase
Rectal Cancer Colon/Rectal Cancer Rectal Cancer Colon/Rectal Cancer	Drug: Oxaliplatin Drug: Capecitabine Drug: Cetuximab	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I/II Trial of Cetuximab in Combination With Oxaliplatin, Capecitabine, and Radiation Therapy Followed by Surgical Resection for Locally-Advanced Rectal Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Oxaliplatin Capecitabine Cetuximab

U.S. FDA Resources

Further study details as provided by Stanford University:

Primary Outcome Measures:

To determine the MTD and DLTs of oxaliplatin and capecitabine when combined with C225 and radiotherapy (Phase I) [ Time Frame: unknown ] [ Designated as safety issue: Yes ]
o determine the pathologic response rate, at the time of surgical resection, of C225 in combination with this neoadjuvant cytotoxic regimen (Phase II). [ Time Frame: unknown ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine the effect of EGFR inhibition on immunohistochemical markers of downstream pathways [ Time Frame: unknown ] [ Designated as safety issue: No ]
To determine additional efficacy endpoints including downstaging, local relapse rate and survival, and time-to-progression in patients treated with the treatment regimen [ Time Frame: unknown ] [ Designated as safety issue: No ]
To determine the toxicity associated with this treatment and to document perioperative morbidity. [ Time Frame: unknown ] [ Designated as safety issue: Yes ]

Enrollment:	23
Study Start Date:	June 2004
Study Completion Date:	February 2009
Primary Completion Date:	March 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: first cohort C225 Oxaliplatin D 2 and 23 Capecitabine XRT	Drug: Oxaliplatin Oxaliplatin is supplied as freeze-dried powder for IV infusion in vials containing 50 mg and 100 mg of the drug. Drug: Capecitabine The calculated dose by cohort designation and body surface area (BSA) will be rounded down to allow equivalent morning and evening doses using a combination of 150 mg and 500 mg tablets. Other Name: C225 Drug: Cetuximab Cetuximab may be administered via a gravity drip, infusion pump or syringe pump with in-line filtration. Cetuximab requires in-line filtration during administration. Calculate and draw the appropriate volume of cetuximab into a sterile syringe based on either the 400 mg/m2 initial dose or 250 mg/m2 weekly dose
Experimental: Second cohort C225 Oxaliplatin D 2 and 23 Capecitabine XRT	Drug: Oxaliplatin Oxaliplatin is supplied as freeze-dried powder for IV infusion in vials containing 50 mg and 100 mg of the drug. Drug: Capecitabine The calculated dose by cohort designation and body surface area (BSA) will be rounded down to allow equivalent morning and evening doses using a combination of 150 mg and 500 mg tablets. Other Name: C225 Drug: Cetuximab Cetuximab may be administered via a gravity drip, infusion pump or syringe pump with in-line filtration. Cetuximab requires in-line filtration during administration. Calculate and draw the appropriate volume of cetuximab into a sterile syringe based on either the 400 mg/m2 initial dose or 250 mg/m2 weekly dose
Experimental: third cohort C225 Oxaliplatin D 2 and 23 Capecitabine XRT	Drug: Oxaliplatin Oxaliplatin is supplied as freeze-dried powder for IV infusion in vials containing 50 mg and 100 mg of the drug. Drug: Capecitabine The calculated dose by cohort designation and body surface area (BSA) will be rounded down to allow equivalent morning and evening doses using a combination of 150 mg and 500 mg tablets. Other Name: C225 Drug: Cetuximab Cetuximab may be administered via a gravity drip, infusion pump or syringe pump with in-line filtration. Cetuximab requires in-line filtration during administration. Calculate and draw the appropriate volume of cetuximab into a sterile syringe based on either the 400 mg/m2 initial dose or 250 mg/m2 weekly dose
Experimental: cohort -1 C225 Oxaliplatin D 2 and 23 Capecitabine XR	Drug: Oxaliplatin Oxaliplatin is supplied as freeze-dried powder for IV infusion in vials containing 50 mg and 100 mg of the drug. Drug: Capecitabine The calculated dose by cohort designation and body surface area (BSA) will be rounded down to allow equivalent morning and evening doses using a combination of 150 mg and 500 mg tablets. Other Name: C225 Drug: Cetuximab Cetuximab may be administered via a gravity drip, infusion pump or syringe pump with in-line filtration. Cetuximab requires in-line filtration during administration. Calculate and draw the appropriate volume of cetuximab into a sterile syringe based on either the 400 mg/m2 initial dose or 250 mg/m2 weekly dose

Eligibility

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

Criteria

Inclusion Criteria:- Patients with histologically confirmed adenocarcinoma of the rectum: EUS stage T3 or T4 or N1 disease are eligible (includes T3 N0, T3 N1, T4 N0, T4 N1, T1-4 N1). Rectal cancers will be defined as those whose distal border extends to within 12cm of the anal verge.

Age >= 18.
Karnofsky performance status >= 70.
Creatinine within normal institutional limits or creatinine clearance > 60mL/min/1.73m2 for patients with serum creatinine levels above institutional normal.
Negative urine pregnancy test if a woman of child bearing potential (WOCBP).
WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study medication.
WOCBP must be using an adequate method of contraception to avoid pregnancy throughout the treatment.
Ability to swallow pills without difficulty.
No prior pelvic or whole abdominal radiotherapy.
Patients must have adequate organ and marrow function as defined below:

Leukocyte count > 3,500. Platelet count > 100,000. SGOT, SGPT, Alk. Phos: < 2.5x institutional upper limits of normal. Total bilirubin < 1.5x institutional normal institutional limits.

Exclusion Criteria:- Metastatic (M1) or stage IV disease.

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Patients with a concurrent malignancy or previous malignancy within 5 years of screening will be excluded from this study; with the exception of patients with concurrent or previous non-melanoma skin cancer, hematolymphoid malignancy or carcinoma in-situ of the cervix, who may be included at the investigator's discretion.
WOCBP who is pregnant or breastfeeding.
A history of C225 or other therapy that targeted the EGF receptor.
A history of prior anti-cancer murine monoclonal antibody therapy.
Inability to sign written consent.
WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks after the study. Subjects who are men must also agree to use effective contraception.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00226941

Locations

United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305

Sponsors and Collaborators

George Albert Fisher

Bristol-Myers Squibb

Investigators

Principal Investigator:	Branimir I Sikic	Stanford University
Principal Investigator:	George Albert Fisher M.D. Ph.D.	Stanford University

More Information

No publications provided

Responsible Party:	George Albert Fisher, Associate Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier:	NCT00226941 History of Changes
Other Study ID Numbers:	COR0001, 95054, COR0001
Study First Received:	September 8, 2005
Last Updated:	November 6, 2012
Health Authority:	United States: Institutional Review Board United States: Food and Drug Administration

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
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 May 16, 2013