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

Phase 2
Terminated
Conditions
Metastatic Non-Small Cell Lung Cancer
Interventions
Registration Number
NCT00872482
Lead Sponsor
YM BioSciences
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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
21
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

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1nimotuzumabNimotuzumab (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.
2nimotuzumabA 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.
Primary Outcome Measures
NameTimeMethod
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 examinationweekly infusions during radiotherapy and following radiotherapy until disease progression, unacceptable toxicity or withdrawal of consent.
Secondary Outcome Measures
NameTimeMethod
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

Trial Locations

Locations (15)

Florida Cancer Institute - New Hope

🇺🇸

New Port Richey, Florida, United States

Park Nicollet Institute - Frauenshuh Cancer Center

🇺🇸

St. Louis Park, Minnesota, United States

Cancer Centre for the Southern Interior

🇨🇦

Kelowna, British Columbia, Canada

London Regional Cancer Center

🇨🇦

London, Ontario, Canada

Overlake Hospital Medical Center

🇺🇸

Bellevue, Washington, United States

Royal Victoria Hospital

🇨🇦

Barrie, Ontario, Canada

Princess Margaret Hospital

🇨🇦

Toronto, Ontario, Canada

Hopital Maisonneuve-Rosemont

🇨🇦

Montreal, Quebec, Canada

Hameed Latif Hospital, Lahore (HLH)

🇵🇰

Town, Lahore, Pakistan

Severance Hospital

🇰🇷

Seoul, Korea, Republic of

Nuclear Medicine and Radiation Oncology Institute (NORI)

🇵🇰

Islamabad, Pakistan

Dr. H. Bliss Murphy Cancer Centre

🇨🇦

St. John's, Newfoundland and Labrador, Canada

Hotel Dieu Hospital

🇨🇦

Quebec City, Quebec, Canada

Hospital Clínico Quirúrgico Hermanos Ameijeiras

🇨🇺

Centro Habana, La Habana, Cuba

Tom Baker Cancer Center

🇨🇦

Calgary, Alberta, Canada

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