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

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Non-small-cell Lung Cancer

Intervention / Treatment
-----------------
* Procedure: External radiotherapy
* Biological: nimotuzumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Patients must have histologically or cytologically confirmed non-small cell lung cancer. Patients must be suitable for palliative radiation therapy as per institutional standards. Stage IIB, III or IV (patients off steroids with treated, stable brain metastases are eligible). Patients may be symptomatic or asymptomatic from disease Age >18 years ECOG 0-1-2 Patients who received previous chemotherapy are allowed Haemoglobin >9g/dL (blood transfusion to increase Hb level is acceptable) 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. Patients must have measurable disease in the planned radiation field. Women of child-bearing potential and men must agree to use adequate contraception. Ability to understand and the willingness to sign a written informed consent document Exclusion criteria - Phase I and Phase II: Patients receiving any other investigational agents Previous treatment with anti-EGF-R drug(s) History of allergic reactions attributed to compounds of similar chemical or biologic composition to nimotuzumab or other agents used in study. Prior thoracic radiotherapy for this condition Prior chemotherapy within 4 weeks of enrolment Lesions not suitable for radiotherapy Patients with known sero positive HIV Patients with uncontrolled hypercalcemia Patients with progressive or untreated brain metastases or treated brain metastases but unable to discontinue steroids 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 Pregnant or breast-feeding women 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 Life expectancy of less than 8 weeks

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
-----------------
Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Progression-free survival |  | 1 year | 
| Phase II: Quality of life |  | At week 4, week 8, every 2 months thereafter | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Non small cell lung cancer, NSCLC, Nimotuzumab, TheraCIM, h-R3, YM BioSciences, Radiation, Non small cell lung cancer, Stage IIb, III and IV