A Study of Nimotuzumab in Combination With Radiation Therapy in Patients With Brain Metastases

A Randomized, Phase II, Double-Blind Study of Nimotuzumab Plus Whole-Brain Radiation Therapy (WBRT) Compared With WBRT Alone in Patients With Brain Metastases From Non-Small Cell Lung Cancer

This is a randomized, Phase II study designed to investigate Nimotuzumab plus whole-brain radiation therapy (WBRT)and to compare it rith WBRT alone in patients with brain metastases from non-small cell lung cancer (NSCLC). The purpose of the study is to assess the efficacy of nimotuzumab in combination with WBRT.

Study Overview

• Status: Terminated
• Conditions: Metastatic Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: nimotuzumab

Detailed Description

A phase II, randomized, controlled, double blinded and multicenter study with 2 arms, administering the study drug during radiotherapy and following radiotherapy until disease progression, unacceptable toxicity or at the discretion of the physician. Randomization will be done 2:1 (experimental:control). Chemotherapy can be added before documented disease progression at the discretion of the physician.

The primary objective is to assess the efficacy of Nimotuzumab in combination with WBRT. The primary endpoint is intracranial disease progression over 6 months.

The secondary endpoints are overall survival (OS); time to neurologic progression (TNP) or death with evidence of neurologic progression; OS rate at 6 months; time to intracranial disease progression; and time to overall progression.

Tissue samples and serum will be collected for future correlative studies.

All the images will be centrally reviewed at the end of study.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N4N2
      • 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
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Hospital
    • London, Ontario, Canada, N6A-4L6
      • London Regional Cancer Center
    • Toronto, Ontario, Canada, M5G-2M9
      • Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H1T-2M4
      • Hopital Maisonneuve-Rosemont
    • Quebec City, Quebec, Canada, G1H 2J6
      • Hotel Dieu Hospital
• Cuba
  • La Habana
    • Centro Habana, La Habana, Cuba
      • Hospital Clínico Quirúrgico Hermanos Ameijeiras
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Severance Hospital
• Pakistan
  • Islamabad, Pakistan
    • Nuclear Medicine and Radiation Oncology Institute (NORI)
  • Lahore
    • Town, Lahore, Pakistan
      • Hameed Latif Hospital, Lahore (HLH)
• United States
  • Florida
    • New Port Richey, Florida, United States, 34655
      • Florida Cancer Institute - New Hope
  • Minnesota
    • St. Louis Park, Minnesota, United States, 55426
      • Park Nicollet Institute - Frauenshuh Cancer Center
  • Washington
    • Bellevue, Washington, United States, 98004
      • Overlake Hospital Medical Center

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

Inclusion Criteria:

• Providing a written informed consent (see Appendix A);
• Age ≥18 years;
• Histologic or cytologic confirmed diagnosis of NSCLC of any epithelial type (squamous, adenocarcinoma, large cell, or other);
• At least one newly diagnosed measurable metastatic lesion from NSCLC in the brain;
• Patient had initial diagnosis of brain metastases by image, within 8 weeks of registration
• KPS ≥70;
• Absolute neutrophil count ≥ 1500/mm³;
• Platelet count ≥ 50,000/mm³;
• Serum creatinine ≤2.0 mg/dL;
• Serum transaminases ≤2 x the upper limit of normal (ULN);
• Total serum bilirubin ≤2 x ULN;
• And a lactate dehydrogenase (LDH) level ≤1.3 x ULN.

Exclusion Criteria:

• Pregnancy, lactation or parturition within the previous 30 days (fertile female or male patients should practice contraception);
• Prior WBRT, brain metastases resection with no other measurable lesion remaining;
• Extracranial metastases in two or more organs;
• Known leptomeningeal or subarachnoid tumor spread;
• Plan to use radiosurgery or radiation boost after completion of WBRT;
• Plan to use chemotherapy or any other systemic antineoplastic modality during WBRT;
• Previous use of an anti-EGFR drug;
• Participation in another ongoing therapeutic trial;
• Presence of known HIV seropositivity, severe comorbidities, or other malignant neoplasm within 5 years (except adequately treated basal- or squamous-cell carcinoma of skin or in situ carcinoma of the uterine cervix);
• Hypersensitivity or allergy to any of the drugs to be administered in this study;
• Inability or unwillingness to complete the required assessments;
• Geographic inaccessibility for treatment or follow-up evaluations.

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
Experimental: 1; Nimotuzumab (200 mg fixed dose) will be administered by the intravenous route weekly during WBRT and following WBRT. Radiotherapy will consist of 30 Gy, in 10 fractions of 3 Gy/day.	Drug: nimotuzumab; Nimotuzumab (200 mg fixed dose) will be administered by the intravenous route weekly during WBRT and following WBRT Radiotherapy will consist of 30 Gy, in 10 fractions of 3 Gy/day.
Placebo Comparator: 2; A placebo will be administered by the intravenous route weekly during WBRT and following WBRT. Radiotherapy will consist of 30 Gy, in 10 fractions of 3 Gy/day.	Drug: nimotuzumab; Nimotuzumab (200 mg fixed dose) will be administered by the intravenous route weekly during WBRT and following WBRT Radiotherapy will consist of 30 Gy, in 10 fractions of 3 Gy/day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase II: efficacy.Withhold of intracranial progression at 2, 4 and 6 months in comparison with control arm. Patients will be assessed by lab tests, MRI,neurologic examination	weekly infusions during radiotherapy and following radiotherapy until disease progression, unacceptable toxicity or withdrawal of consent.

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS); time to neurologic progression (TNP) or death with evidence of neurologic progression; OS rate at 6 months; time to intracranial disease progression; and time to overall progression.	1 year

Collaborators and Investigators

• Sponsor: YM BioSciences
• Collaborators: CIMYM BioSciences
• Investigators: Principal Investigator: Anthony Brade, M.D., Assitant Professor, Department of Radiation Oncology, University of Toronto

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: March 26, 2009
• First Submitted That Met QC Criteria: March 30, 2009
• First Posted (Estimate): March 31, 2009

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; Brain metastases; TheraCIM; h-R3
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Brain Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Nimotuzumab
• Other Study ID Numbers: YMB1000-018