A Study of Nimotuzumab in Combination With Radiation Therapy in Patients With Brain Metastases - Full Text View

Purpose

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.

Condition	Intervention	Phase
Metastatic Non-Small Cell Lung Cancer	Drug: nimotuzumab	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

U.S. FDA Resources

Further study details as provided by YM BioSciences:

Primary Outcome Measures:

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 [ Time Frame: weekly infusions during radiotherapy and following radiotherapy until disease progression, unacceptable toxicity or withdrawal of consent. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment:	21
Study Start Date:	April 2009
Estimated Study Completion Date:	July 2011
Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00872482

Locations

United States, Florida
Florida Cancer Institute - New Hope
New Port Richey, Florida, United States, 34655
United States, Minnesota
Park Nicollet Institute - Frauenshuh Cancer Center
St. Louis Park, Minnesota, United States, 55426
United States, Washington
Overlake Hospital Medical Center
Bellevue, Washington, United States, 98004
Canada, Alberta
Tom Baker Cancer Center
Calgary, Alberta, Canada, T2N4N2
Canada, British Columbia
Cancer Centre for the Southern Interior
Kelowna, British Columbia, Canada, V1Y 5L3
Canada, Newfoundland and Labrador
Dr. H. Bliss Murphy Cancer Centre
St. John's, Newfoundland and Labrador, Canada, A1B 3V6
Canada, Ontario
Royal Victoria Hospital
Barrie, Ontario, Canada, L4M 6M2
London Regional Cancer Center
London, Ontario, Canada, N6A-4L6
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G-2M9
Canada, Quebec
Hopital Maisonneuve-Rosemont
Montreal, Quebec, Canada, H1T-2M4
Hotel Dieu Hospital
Quebec City, Quebec, Canada, G1H 2J6
Cuba
Hospital Clínico Quirúrgico Hermanos Ameijeiras
Centro Habana, La Habana, Cuba
Korea, Republic of
Severance Hospital
Seoul, Korea, Republic of
Pakistan
Hameed Latif Hospital, Lahore (HLH)
Town, Lahore, Pakistan
Nuclear Medicine and Radiation Oncology Institute (NORI)
Islamabad, Pakistan

Sponsors and Collaborators

YM BioSciences

CIMYM BioSciences

Investigators

Principal Investigator:

Anthony Brade, M.D.

Assitant Professor, Department of Radiation Oncology, University of Toronto

More Information

No publications provided

Responsible Party:	Wendy Chapman, Vice President, Clinical Operations, YM BioSciences
ClinicalTrials.gov Identifier:	NCT00872482 History of Changes
Other Study ID Numbers:	YMB1000-018
Study First Received:	March 26, 2009
Last Updated:	June 30, 2011
Health Authority:	Canada: Health Canada Canada: Ethics Review Committee

Keywords provided by YM BioSciences:

non-small cell lung cancer
NSCLC
Brain metastases
nimotuzumab

TheraCIM
h-R3
Radiation

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasm Metastasis
Brain Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms

Lung Diseases
Respiratory Tract Diseases
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on May 22, 2013