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

Metastatic Non-Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00872482
• Other study ID #: YMB1000-018
• Status: Terminated
• Phase: Phase 2
• First received: March 26, 2009
• Last updated: June 30, 2011
• Start date: April 2009
• Est. completion date: July 2011

Study information

• Verified date: June 2011
• Source: YM BioSciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaCanada: Ethics Review Committee
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: July 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Metastatic Non-Small Cell Lung Cancer

Intervention

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.

Locations

Country	Name	City	State
Canada	Royal Victoria Hospital	Barrie	Ontario
Canada	Tom Baker Cancer Center	Calgary	Alberta
Canada	Cancer Centre for the Southern Interior	Kelowna	British Columbia
Canada	London Regional Cancer Center	London	Ontario
Canada	Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Hotel Dieu Hospital	Quebec City	Quebec
Canada	Dr. H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador
Canada	Princess Margaret Hospital	Toronto	Ontario
Cuba	Hospital Clínico Quirúrgico Hermanos Ameijeiras	Centro Habana	La Habana
Korea, Republic of	Severance Hospital	Seoul
Pakistan	Nuclear Medicine and Radiation Oncology Institute (NORI)	Islamabad
Pakistan	Hameed Latif Hospital, Lahore (HLH)	Town	Lahore
United States	Overlake Hospital Medical Center	Bellevue	Washington
United States	Florida Cancer Institute - New Hope	New Port Richey	Florida
United States	Park Nicollet Institute - Frauenshuh Cancer Center	St. Louis Park	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
YM BioSciences	CIMYM BioSciences

Countries where clinical trial is conducted

United States,  Canada,  Cuba,  Korea, Republic of,  Pakistan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Yes
Secondary	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	No