Clinical trial NCT00872482: A Study of Nimotuzumab in Combination With Radiation Therapy in Patients With Brain Metastases
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Metastatic Non-Small Cell Lung Cancer
Keywords: non-small cell lung cancer
NSCLC
Brain metastases
nimotuzumab
TheraCIM
h-R3
Radiation
Lead sponsor: YM BioSciences
Sponsor class: INDUSTRY
Collaborators: name: CIMYM BioSciences
First posted: 2009-03-31
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
measure: 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
timeFrame: weekly infusions during radiotherapy and following radiotherapy until disease progression, unacceptable toxicity or withdrawal of consent.
Secondary outcomes:
measure: 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.
timeFrame: 1 year
Other outcomes:
Locations:
city: New Port Richey
country: United States
facility: Florida Cancer Institute - New Hope
state: Florida
city: St. Louis Park
country: United States
facility: Park Nicollet Institute - Frauenshuh Cancer Center
state: Minnesota
city: Bellevue
country: United States
facility: Overlake Hospital Medical Center
state: Washington
city: Calgary
country: Canada
facility: Tom Baker Cancer Center
state: Alberta
city: Kelowna
country: Canada
facility: Cancer Centre for the Southern Interior
state: British Columbia
city: St. John's
country: Canada
facility: Dr. H. Bliss Murphy Cancer Centre
state: Newfoundland and Labrador
city: Barrie
country: Canada
facility: Royal Victoria Hospital
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Center
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Hopital Maisonneuve-Rosemont
state: Quebec
city: Quebec City
country: Canada
facility: Hotel Dieu Hospital
state: Quebec
city: Centro Habana
country: Cuba
facility: Hospital Clínico Quirúrgico Hermanos Ameijeiras
state: La Habana
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Town
country: Pakistan
facility: Hameed Latif Hospital, Lahore (HLH)
state: Lahore
city: Islamabad
country: Pakistan
facility: Nuclear Medicine and Radiation Oncology Institute (NORI)
Study officials:
affiliation: Assitant Professor, Department of Radiation Oncology, University of Toronto
name: Anthony Brade, M.D.
role: PRINCIPAL_INVESTIGATOR
References: