Comparison Study of WBRT and SRS Alone Versus With Temozolomide or Erlotinib in Patients With Brain Metastases of NSCLC

A Phase III Trial Comparing Whole Brain Radiation (WBRT) and Stereotactic Radiosurgery (SRS) Alone Versus With Temozolomide or Erlotinib in Patients With Non-Small Cell Lung Cancer and 1-3 Brain Metastases

The objectives of the study is to determine if either temozolomide or erlotinib combined with WBRT and SRS improves survival as compared to WBRT and SRS alone.Ptients with histologically confirmed NSCLC with the presence of 1-3 intraparenchymal brain metastases will be randomized to 3 arms. All of the patients will receive WBRT and SRS. The patients of the arm 1 will receive radiation treatment only, the arm 2 patients will be treated with temozolomide and arm 3 patients will receive erlotinib

Study Overview

• Status: Unknown
• Conditions: Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis
• Intervention / Treatment: Drug: Erlotinib, Temozolomide

• Study Type: Interventional
• Enrollment: 381
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Lina Veisenman; Phone Number: 972-36977285
• Study Contact Backup: Name: Felix Bokstein, M.D.; Phone Number: 972-524266532; Email: fbok@netvision.net.il

Study Locations

• Israel
  • Tel Aviv, Israel, 63409
    • Recruiting
    • Tel Aviv Sourasky Medical Center
    • Contact: Felix Bokstein, M.D.; Phone Number: 972-524266532; Email: fbok@netvision.net.il
    • Contact: Debora Blumenthal, M.D.; Phone Number: 972-524266403; Email: dvorab@tasmc.gov.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically confirmed non-small cell lung cancer with the presence of 1-3 intraparenchymal brain metastases.
2. A contrast-enhanced MRI demonstrating the presence of 1-3 brain metastases performed within two weeks prior to registration.
3. The contrast-enhancing intraparenchymal brain tumor must be well circumscribed and must have a maximum diameter of ≤ 4.0 cm in any direction on the enhanced scan. If multiple lesions are present and one lesion is at the maximum diameter, the other(s) must not exceed 3.0 cm in maximum diameter.
4. Patients who present with symptoms of brain metastases at the time of initial diagnosis are eligible and do not need to demonstrate one month of stable scans.
5. Age 18 years or older.
6. Zubrod 0-1
7. Neurologic Function Status 0, 1, or 2.
8. Patients may have stable extracranial metastases.
9. Contrast-enhancing CT scans of the chest, abdomen and pelvis, and bone scan to determine the extent of extracranial malignant disease.
10. Adequate bone marrow reserve
11. Patients randomized to receive erlotinib who are on enzyme inducing seizure medicines including phenytoin, carbamazepine, rifampicin, barbiturates must be converted to a nonenzyme inducing anti-seizure medication. Patients on Arm 3 will not be able to start treatment immediately if converting.

12. Patient must sign a study-specific informed consent form. If the patient's mental status precludes his/her giving informed consent, written informed consent may be given by the patient's legal representative.

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Exclusion Criteria:

1. Major medical illnesses or psychiatric impairment
2. Patients who have undergone a complete resection of all known brain metastases.Patients who have undergone subtotal resection are eligible providing residual disease is =/< 4.0 cm in maximum diameter.
3. Inability to obtain histologic proof of NSCLC.
4. Patients with leptomeningeal metastases documented by MRI or CSF evaluation.
5. Clinical or radiographic evidence of progression (other than the study lesion(s)) within one month prior to enrollment. (Patients who have brain metastases at initial presentation are eligible and do not need to demonstrate one month of stable scans).
6. Patients with metastases within 10 mm of the optic apparatus so that some portion of the optic nerve or chiasm would be included in the high dose SRS boost field.
7. Patients with metastases in the brainstem, midbrain, pons, or medulla.
8. Patients with liver metastases.
9. Previous cranial radiation.
10. Women who are pregnant or nursing
11. Patients who are HIV positive are not eligible.
12. Any evidence of clinically active interstitial lung disease
13. Treatment with a non-approved or investigational drug within 30 days before Day 1 of studytreatment.
14. Concomitant use of St. John's Wort.
15. History of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib and temozolomide.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure
survival

Collaborators and Investigators

• Sponsor: Tel-Aviv Sourasky Medical Center
• Collaborators: Radiation Therapy Oncology Group
• Investigators: Principal Investigator: Felix Bokstein, M.D., Tel-Aviv Sourasky Medical Center

Study record dates

Study Major Dates

• Study Start: May 1, 2005

Study Registration Dates

• First Submitted: December 21, 2005
• First Submitted That Met QC Criteria: December 21, 2005
• First Posted (Estimate): December 22, 2005

Study Record Updates

• Last Update Posted (Estimate): February 28, 2006
• Last Update Submitted That Met QC Criteria: February 27, 2006
• Last Verified: December 1, 2005

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Brain Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride; Temozolomide
• Other Study ID Numbers: TASMC-05-FB-05235-CTIL