Comparative Study of Cetuximab and Radiation Vs Surgery Before or After Radiation in Patients With Colorectal Carcinoma

• ClinicalTrials.gov Identifier: NCT00725400
• Recruitment Status: Withdrawn
• First Posted: July 30, 2008
• Last Update Posted: July 20, 2011
• Sponsor: American Scitech International
• Collaborators: Eli Lilly and Company; Bristol-Myers Squibb
• Information provided by: American Scitech International

Tracking Information

• First Submitted Date: July 28, 2008
• First Posted Date: July 30, 2008
• Last Update Posted Date: July 20, 2011
• Study Start Date: February 2010
• Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 28, 2008): Objective tumor response rate [ Time Frame: 4 year ]
• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT00725400 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: July 28, 2008)

• Tolerability [ Time Frame: 4 years ]
• Progression free survival [ Time Frame: 4 years ]
• Overall survival [ Time Frame: 4 Years ]
• Quality of life [ Time Frame: 4 Years ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Comparative Study of Cetuximab and Radiation Vs Surgery Before or After Radiation in Patients With Colorectal Carcinoma
• Official Title: Phase II Open Label Comparative Study of Cetuximab and Radiation Therapy Vs Surgery Before or After Radiation Therapy in Patients With Stage II to IV Colorectal Carcinoma

Brief Summary

RATIONALE: Monoclonal antibodies, such as Cetuximab, can target tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.This is an anti-cancer drug which has already been approved by the FDA for use in patients who have Colorectal Cancer. 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. Radiation Therapy uses high-energy x-rays to kill tumor cells and cause less damage to normal tissue . Giving the drug Cetuximab together with Radiation Therapy may kill more tumor cells. Surgery is the most common treatment for Colorectal Cancer to remove the tumor, as well as a small margin of surrounding normal tissue and possibly nearby lymph nodes. Surgery is usually used in conjunction with other conventional treatments such as Radiation Therapy. Radiation Therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Radiation Therapy after surgery may kill any tumor cells that remain after surgery.

Screening test such as Fecal Occult Blood Test (FOBT) and Colonoscopy has to be done. Tumor markers for Colorectal Carcinoma are Carcinoembryonic antigen (CAE) and CA 19-9 and to assess the response of tumor markers Carcinoembryonic antigen (CAE) and CA 19-9 will be used and periodically Colonoscopy has to be done. Colorectal Cancer Surgery are Colon resection (Colectomy), Rectum resection (Proctectomy), Colostomy, and Radiofrequency ablation.

PURPOSE: Determine the tumor response rate treated with Cetuximab and Radiation Therapy Vs Surgery before or after Radiation Therapy in patients with Colorectal Cancer from stage II to IV

Detailed Description

OBJECTIVES:

Primary:

• Determine the response rate in patients with Colorectal Cancer treated with Cetuximab and Radiation Therapy Vs Surgery before or after Radiation Therapy.

Secondary:

• To determine the progression-free survival and overall survival of patients treated with these regimens.
• Compare the treatment compliance of patients treated with these regimens.
• Compare the safety of these regimens in these patients.

OUTLINE: This is an Open-label, Controlled, Multicenter study. Patients will be assigned into two different Arms.

Arm I: Patients will receive Cetuximab and Radiation Therapy. Patients will receive a dose of Cetuximab through Intravenous (IV). The initial dose is 400 mg/m2 administered as a 120-minute intravenous infusion (maximum infusion rate 10 mg/min) and weekly dose is 250 mg/m2 infused over 60 minutes (maximum infusion rate 10 mg/min) until disease progression or unacceptable toxicity. Radiation treatment for Colorectal Cancer are Intensity Modulated Radiation Therapy (IMRT). IMRT delivers radiation directly to the tumor and modulates the intensity of the radiation with laser accuracy.

Arm II: Patients will undergo surgery before or after Radiation Therapy. Colorectal Cancer Surgery are Colon resection (Colectomy), Rectum resection (Proctectomy), Colostomy, and Radiofrequency ablation. Radiation treatment for Colorectal Cancer are Intensity Modulated Radiation Therapy (IMRT). IMRT delivers radiation directly to the tumor and modulates the intensity of the radiation with laser accuracy.

PROJECTED ACCRUAL: Approximately 450 patients will be accrued for this study within 18 to 24 months.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Colorectal Carcinoma

Intervention

• Other: Cetuximab and Radiation Therapy
  Patients will receive Cetuximab and Radiation Therapy. Patients will receive a dose of Cetuximab through Intravenous (IV). The initial dose is 400 mg/m2 administered as a 120-minute intravenous infusion (maximum infusion rate 10 mg/min) and weekly dose is 250 mg/m2 infused over 60 minutes (maximum infusion rate 10 mg/min) until disease progression or unacceptable toxicity. Radiation treatment for Colorectal Cancer are Intensity Modulated Radiation Therapy (IMRT). IMRT delivers radiation directly to the tumor and modulates the intensity of the radiation with laser accuracy.
  Other Name: Erbitux and Radiotherapy
• Procedure: Surgery and Radiation Therapy
  Patients will undergo Surgery before or after Radiation Therapy. Colorectal Cancer Surgery are Colon resection (Colectomy), Rectum resection (Proctectomy), Colostomy, and Radiofrequency ablation. Radiation treatment for Colorectal Cancer are Intensity Modulated Radiation Therapy (IMRT). IMRT delivers radiation directly to the tumor and modulates the intensity of the radiation with laser accuracy.
  Other Name: Surgery and Radiotherapy

Study Arms

• Active Comparator: 1
  Patients will receive a Cetuximab and Radiation Therapy.
  Intervention: Other: Cetuximab and Radiation Therapy
• Active Comparator: 2
  Patients will undergo Surgery before or after Radiation Therapy.
  Intervention: Procedure: Surgery and Radiation Therapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Withdrawn
• Estimated Enrollment (submitted: July 28, 2008): 450
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2014
• Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients with stage II- IV Colorectal Cancer
• Patients must be 40 years and older
• Patients may be of any race and either gender
• Signed Informed Consent

Patient characteristics:

• Age: 40 years and older
• Sex: Both
• Performance status: Not specified
• Life expectancy: Not specified

Hematopoietic:

• Granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL
• No history of significant bleeding events within the past 6 months

Hepatic:

• Bilirubin ≤ 1.5 mg/dL
• Albumin ≥ 2.5 g/dL

Renal:

• Creatinine ≤ 1.5 times upper limit of normal
• Protein < 1+ by urinalysis
• Protein < 1 g by 24-hour urine collection

Cardiovascular:

• No conduction defect in heart
• No congestive heart failure
• No myocardial infarction within last 6 months
• No cerebrovascular accident
• No uncontrolled hypertension
• No clinically significant peripheral artery disease

Pulmonary:

• No pulmonary embolism
• No interstitial pneumonia
• No extensive or symptomatic interstitial fibrosis of the lung

Neurologic:

• No uncontrolled seizure disorder
• No active neurological disease

Other:

• Not pregnant or nursing
• Negative pregnancy test

Exclusion Criteria:

• Age below 40 years
• Brain or nervous system metastases
• Any current mental illness
• Hemoglobin is less than 9.0 g/dl
• CBC results are below normal range
• Patients with Hepatitis B or C or who are HIV positive
• Pregnant or nursing patients are not eligible for entry into the study
• Hepatic abnormality AST/ALT > 4 folds

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00725400
• Other Study ID Numbers: ASI-CRO0000192008; JLRH-0000292008; IORG-0000392008; BMS-192008; IMCL-II-ASI-IORG-92008; ASI-CRCII0708
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Dr. Ratna Grewal, American Scitech International
• Study Sponsor: American Scitech International

Collaborators

• Eli Lilly and Company
• Bristol-Myers Squibb

Investigators

• Study Chair: Ratna Grewal, MD; American Scitech International- eCRO
• Principal Investigator: Prem A Nandiwada, MD; Raritan Bay Medical Center
• Study Director: Sarat Babu, MD; St. Peter's Hospital
• Principal Investigator: S N Agrawal, MD; JLR Hospital in India

• PRS Account: American Scitech International
• Verification Date: July 2011