A Study of Nimotuzumab in Combination With External Radiotherapy in Non-Small Cell Lung Cancer

A Phase I-II Clinical Study of Nimotuzumab (TheraCIM h-R3) in Combination With External Radiotherapy in Stage IIB, III and IV NSCLC

This is a Phase I-II study designed to investigate nimotuzumab (TheraCIM h-R3) in combination with external radiation in patients with non-small cell lung cancer. The purpose of the Phase I portion of the study is to evaluate the safety and feasibility of the administration of nimotuzumab with palliative radiation in patients who are unsuitable for radical therapy and to select the optimal dose for the Phase II component of the study. The primary objective for the Phase II portion of the study is to examine the efficacy of this combination treatment.

The Phase I component of this study has been completed. The Phase II is now closed to recruitment.

Study Overview

• Status: Terminated
• Conditions: Non-small-cell Lung Cancer
• Intervention / Treatment: Procedure: External radiotherapy; Biological: nimotuzumab

Detailed Description

This is a randomized, double blind, multicenter Phase II study with Phase I lead-in. Patients enrolled in this study will receive external radiotherapy with or without nimotuzumab (TheraCIM h-R3). The objective of the Phase I component of the study is to evaluate the safety and feasibility of the administration of nimotuzumab with palliative radiation in patients who are unsuitable for radical therapy (curative intent chemoradiation) and to select the optimal biologically effective dose (BED) for Phase II component of the study. In the Phase II component, overall survival, local and systemic response rates and quality of life will be evaluated inpatients treated with nimotuzumab in combination with palliative radiation vs. radiation alone.

The Phase I component of this study has been completed. The Phase II is now closed to recruitment.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Center
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • Cancer Centre for the Southern Interior
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Dr. H. Bliss Murphy Cancer Centre
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Center
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital Cancer Centre
    • Thunderbay, Ontario, Canada, P7B 6V4
      • Thunderbay Regional hospital Center
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • Centre Hospitalier de l'Université de Montréal - Hôpital Notre Dame
    • Montreal, Quebec, Canada, H1T-2M4
      • Hôpital Maisonneuve-Rosemont
    • Montreal, Quebec, Canada, H3T 1E2
      • Segal Cancer Center - Jewish General Hospital
    • Quebec City, Quebec, Canada, G1R 2J6
      • Hotel Dieu Hospital
• Singapore
  • Singapore, Singapore, 160610
    • National Cancer Center Singapore
• United States
  • Florida
    • New Port Richey, Florida, United States, 34655
      • Florida Cancer Institute - New Hope

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

1. Patients must have histologically or cytologically confirmed non-small cell lung cancer.
2. Patients must be suitable for palliative radiation therapy as per institutional standards.
3. Stage IIB, III or IV (patients off steroids with treated, stable brain metastases are eligible).
4. Patients may be symptomatic or asymptomatic from disease
5. Age >18 years
6. ECOG 0-1-2
7. Patients who received previous chemotherapy are allowed
8. Haemoglobin >9g/dL (blood transfusion to increase Hb level is acceptable)
9. Stage II/III patients must be considered unsuitable for radical (standard full dose curative intent) chemoradiation in the opinion of either the radiotherapist or medical oncologist.
10. Patients must have measurable disease in the planned radiation field.
11. Women of child-bearing potential and men must agree to use adequate contraception.
12. Ability to understand and the willingness to sign a written informed consent document

Exclusion criteria - Phase I and Phase II:

1. Patients receiving any other investigational agents
2. Previous treatment with anti-EGF-R drug(s)
3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to nimotuzumab or other agents used in study.
4. Prior thoracic radiotherapy for this condition
5. Prior chemotherapy within 4 weeks of enrolment
6. Lesions not suitable for radiotherapy
7. Patients with known sero positive HIV
8. Patients with uncontrolled hypercalcemia
9. Patients with progressive or untreated brain metastases or treated brain metastases but unable to discontinue steroids
10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, severe cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements in the opinion of the investigator
11. Pregnant or breast-feeding women
12. Any concurrent active malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix; patients with other prior malignancies are eligible providing prior malignancy cannot be clinically confused with the diagnosis of NSCLC in the opinion of the treating oncologist; in particular, there should be no evidence of current disease activity with respect to the prior malignancy
13. Life expectancy of less than 8 weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2	Procedure: External radiotherapy; Radiotherapy for first 2 weeks, 10 daily fractions of 30Gy 2 additional fractions to be added if desirable; Biological: nimotuzumab; weekly dose until disease progression
Experimental: 1; 200 mg dose	Procedure: External radiotherapy; Radiotherapy for first 2 weeks, 10 daily fractions of 30Gy 2 additional fractions to be added if desirable; Biological: nimotuzumab; weekly dose until disease progression

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase II: Overall survival	Every 8 weeks until disease progression

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	1 year
Phase I: Biologically effective dose	2.5 Years
Phase II: Overall response rate	Every 8 weeks until disease progression
Local response rate	Every 8 weeks until disease progression
Overall clinical benefit	Every 8 weeks until disease progression
Local clinical benefit	Every 8 weeks until disease progression
Time to progression	Every 8 weeks until disease progression
Time to local progression	Every 8 weeks until disease progression
Phase II: Quality of life	At week 4, week 8, every 2 months thereafter

Collaborators and Investigators

• Sponsor: YM BioSciences
• Collaborators: CIMYM BioSciences
• Investigators: Principal Investigator: Gwyn Bebb, MD, Tom Baker Cancer Center; Principal Investigator: Anthony Brade, MD, Princess Margaret Hospital, Canada

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): June 1, 2011
• Study Completion (Anticipated): July 1, 2011

Study Registration Dates

• First Submitted: August 24, 2006
• First Submitted That Met QC Criteria: August 24, 2006
• First Posted (Estimate): August 29, 2006

Study Record Updates

• Last Update Posted (Estimate): July 1, 2011
• Last Update Submitted That Met QC Criteria: June 30, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: NSCLC; Non small cell lung cancer; Radiation; Nimotuzumab; TheraCIM; h-R3; YM BioSciences; Non small cell lung cancer, Stage IIb, III and IV
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Antineoplastic Agents, Immunological; Nimotuzumab
• Other Study ID Numbers: YMB1000-010