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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Metastatic Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: nimotuzumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>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<br>* 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.<br>|
| Placebo Comparator: 2<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-small cell lung cancer, NSCLC, Brain metastases, nimotuzumab, TheraCIM, h-R3, Radiation