Study of Nimotuzumab and Irinotecan in Metastatic Colorectal Cancer

NCT00493857 | Terminated Phase 2 DMC

• 1 other identifier: YMB 1000-015
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 12

Brief Summary

This study will determine if nimotuzumab provides a benefit in this type of cancer when given in combination with irinotecan. The study will test:

• How long any good effects last.
• How bad any side effects are. Objectives: Primary: The primary goal is to assess the Objective Response Rate (ORR) that the combination of irinotecan and nimotuzumab will produce in patients with irinotecan-refractory metastatic colorectal cancer Secondary:
• To assess the incidence of Grade 2 or greater acneiform rash or infusion reaction, allergic reaction or anaphylactoid reaction AEs in patients with irinotecan-refractory metastatic colorectal cancer following weekly or 2-weekly nimotuzumab schedules;
• To assess Progression-Free Survival (PFS), defined as time from date of randomization until date of disease progression (clinical or radiological) or death due to any cause, for the two nimotuzumab schedules;
• To assess the rates and durations of Stable Disease (SD) following weekly or 2-weekly nimotuzumab schedules;
• To assess the Time to Disease Progression (TTP) following weekly or 2-weekly nimotuzumab schedules;
• To evaluate ORR in patients who are identified as having "primary" irinotecan resistance following weekly or 2-weekly nimotuzumab schedules;
• To evaluate Overall Survival (OS) following weekly or 2-weekly nimotuzumab schedules;
• To compare the two dosing schedules of nimotuzumab with respect to objective response rates and safety;
• To evaluate the overall safety and toxicity profiles of these two dose regimens of nimotuzumab;
• To evaluate trough levels and accumulation of nimotuzumab in serum of patients receiving the drug on weekly or 2-weekly regimens.

Conditions

Colorectal Cancer

Keywords

Colorectal cancer; Monoclonal antibody; Anti-EGFR

Outcome Measures

Primary Outcomes (1)

• The primary goal is to assess the Objective Response Rate (ORR) that the combination of irinotecan and nimotuzumab will produce in patients with irinotecan-refractory metastatic colorectal cancer

  18-24 months

Secondary Outcomes (1)

• Assess the incidence of acneiform rash,drug reaction,adverse events, the assessment of progression-free survival,stable disease,time to disease progression, overall survival, objective response rates, safety and trough levels in the serum of patients.

  18-24 months

Study Arms (1)

2

EXPERIMENTAL

Nimotuzumab 400mg every week or every two weeks

Drug: Nimotuzumab Humanized Monoclonal Antibody; Drug: Nimotuzumab

Interventions

Nimotuzumab Humanized Monoclonal Antibody DRUG

Nimotuzumab 400mg every week

2

Nimotuzumab DRUG

Nimotuzumab 400mg every 2 weeks

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed colorectal cancer with metastatic disease documented on diagnostic imaging studies.
• Measurable disease,
• Must have clinical documentation of failure after receiving at least one chemotherapy regimen for metastatic disease that contained irinotecan.
• Must have documentation of failure by CT, MRI or PET scan. Patients who were intolerant of irinotecan despite dose attenuations are not eligible for this trial.
• Patients must have failed irinotecan which they received on one of the following three starting regimens:Weekly,Biweekly or every 3 weeks. mg/m2.
• Patients may have received any number of prior standard and investigational regimens or radiation treatments, provided that they meet all other eligibility criteria.
• Age greater than 18 years.
• Life expectancy of greater than 3 months.
• ECOG performance status less than 1
• Patients must have normal organ and marrow function
• Patients must have medical documentation of dose, schedule, and dates of last irinotecan administration.
• Women of child-bearing potential and men must agree to use adequate contraception
• Patients must have the ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Neurotoxicity, if present, must have recovered to \< grade 2.
• No other investigational agents.
• No known brain metastases.Patients with a history of primary CNS tumours, seizures not well controlled with standard medical therapy, or history of stroke will also be excluded.
• History of allergic reactions attributed to compounds of chemical or biologic composition similar to nimotuzumab, irinotecan, or other agents used in the study.
• Previous EGFR-directed therapy
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled hypertension, clinically significant cardiac arrhythmia, history of myocardial infarction within the past 6 months, or psychiatric illness/social situations that would limit compliance with study requirements.
• HIV-positive patients on combination antiretroviral therapy are ineligible
• Active cardiovascular disease, e.g., uncontrolled hypertension, unstable angina, New York Heart Association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medications, or grade II or greater peripheral vascular disease. In addition, patients with arterial thrombosis, myocardial infarction, and cerebral vascular accidents \[stroke/transient ischemic attack (TIA)\] within 6 months prior to study entry will be excluded.
• Organ allografts requiring immunosuppressive therapy. -.Pregnant or lactating women are excluded from this study.

Sponsors & Collaborators

• YM BioSciences: lead

Study Sites (12)

Tom Baker Cancer Center

Calgary, Alberta, T2N 4N2, Canada

Location

Cancer Care Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Dr. H. Bliss Purphy Cancer Centre

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

Royal Victoria Hospital

Barrie, Ontario, L4M 6M2, Canada

Location

Grand River Hospital

Kitchener, Ontario, N2G 1G3, Canada

Location

London Regional Cancer Centre

London, Ontario, N6A 4L6, Canada

Location

Credit Valley Hospital /Carlo Fidani Peel Regional Cancer Centre

Mississauga, Ontario, L5M 2N1, Canada

Location

Cancer Care Program Southlake Regional Health Centre

Newmarket, Ontario, Canada

Location

Ottawa Regional Cancer Centre

Ottawa, Ontario, K1H 1C4, Canada

Location

Algoma District Cancer Care Program

Sault Ste. Marie, Ontario, P6A 2C4, Canada

Location

Sunnybrook Regional Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

nimotuzumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Amil Shah, MD

  Vancouver Cancer Centre BC cancer Agency

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: June 27, 2007
• First Posted: June 28, 2007
• Study Start: June 1, 2007
• Primary Completion: August 1, 2008
• Study Completion: December 1, 2008
• Last Updated: November 17, 2008

Record last verified: 2008-11

Locations

CA (12)