Stereotactic Radiosurgery and Erlotinib in Treating Patients With Non-Small Cell Lung Cancer and Brain Metastases

NCT00738335 | Withdrawn Phase 1 DMC

• 4 other identifiers: CDR0000612064UCSF-072520CC# 072520GENENTECH-UCSF-072520
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Stereotactic radiosurgery may be able to deliver x-rays directly to the tumor and cause less damage to normal tissue. Erlotinib may make tumor cells more sensitive to radiation therapy. Giving erlotinib together with stereotactic radiosurgery may kill more tumor cells. PURPOSE: This phase I clinical trial is studying the side effects of erlotinib when given together with stereotactic radiosurgery and to see how well it works in treating patients with non-small cell lung cancer with brain metastases.

Conditions

Lung Cancer; Metastatic Cancer

Keywords

stage IV non-small cell lung cancer; tumors metastatic to brain; recurrent non-small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• Acute and long-term toxicity (i.e., neurotoxicity, gastrointestinal, cutaneous, and hematologic) as assessed by NCI CTCAE v3.0.

Secondary Outcomes (6)

• Disease progression

• Response rate of radiosurgically treated lesions in patients receiving concurrent erlotinib hydrochloride and radiosurgery on this study vs the response rate of historical controls previously treated with gamma knife radiosurgery alone

• CNS progression at 1 year

• Distribution of erlotinib hydrochloride in plasma and cerebrospinal fluid (CSF)

• CSF and serum biomarkers

Interventions

erlotinib hydrochloride DRUG

immunoenzyme technique OTHER

laboratory biomarker analysis OTHER

liquid chromatography OTHER

mass spectrometry OTHER

pharmacological study OTHER

stereotactic radiosurgery RADIATION

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed non-small cell lung cancer (NSCLC) meeting the following criteria: * Fewer than 5 intraparenchymal brain metastases by gadolinium-enhanced MRI meeting the following criteria: * Maximum diameter ≤ 4.0 cm * If multiple lesions are present and one lesion is \> 3.0 cm, the remaining lesions must be ≤ 3.0 cm in maximum diameter * No metastases within 3 mm of the optic nerve or optic chiasm such that some portion of the optic nerve or chiasm would receive \> 9 Gy from radiosurgery * No metastases in the brainstem, midbrain, pons, or medulla * No prior complete resection of a single brain metastasis or of all known brain metastases * Subtotal resection allowed provided residual disease is ≤ 4.0 cm in maximum diameter * No clinical or radiographic evidence of unstable systemic progression (other than the study lesion\[s\]) within the past month * Patients with brain metastases at initial presentation do not require 1 month of scans documenting stable disease * Isolated brain metastases with stable systemic disease allowed * No leptomeningeal metastases by MRI and/or positive cerebrospinal fluid cytology PATIENT CHARACTERISTICS: * Karnofsky performance status 60-100% * Life expectancy ≥ 3 months * ANC \> 1,000/mm³ * Platelet count \> 100,000/mm³ * Hemoglobin \> 10 g/dL * PT and PTT normal * AST \< 2 times upper limit of normal (ULN) * Alkaline phosphatase \< 2 times ULN * Total bilirubin \< 2 times ULN * Lactic dehydrogenase \< 2 times ULN * Serum creatinine \< 1.5 times ULN * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for ≥ 2 weeks after completion of study therapy * Neurologic function status 0-2 * No history of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib hydrochloride * No contraindication to MRI (e.g., cardiac pacemaker) * No absolute contraindication to lumbar puncture PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Prior systemic therapy allowed * No prior cranial radiotherapy * Prior radiotherapy to noncranial sites allowed * More than 1 week since prior intrathecal chemotherapy or prior treatment of leptomeningeal carcinoma * No concurrent systemic therapy * Prior or current erlotinib hydrochloride for treatment of systemic disease allowed provided systemic disease has not progressed while on erlotinib hydrochloride * No concurrent enzyme-inducing anticonvulsant * If patients are on an enzyme-inducing anticonvulsant (e.g., phenytoin, carbamazepine, or phenobarbital), the agent must be converted to a nonenzyme-inducing anticonvulsant before or at the start of erlotinib hydrochloride treatment * No concurrent CYP3A4 inhibitors or inducers (e.g., Hypericum perforatum \[St. John wort\] or ketoconazole) * No other concurrent investigational therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

MeSH Terms

Conditions

Lung Neoplasms; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Interventions

Erlotinib Hydrochloride; Immunoenzyme Techniques; Chromatography, Liquid; Mass Spectrometry; Radiosurgery

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Immunoassay; Immunologic Techniques; Investigative Techniques; Immunohistochemistry; Molecular Probe Techniques; Chromatography; Chemistry Techniques, Analytical; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative

Study Officials

• James L. Rubenstein, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2008
• First Posted: August 20, 2008
• Study Start: January 1, 2009
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: October 4, 2012

Record last verified: 2012-10

Locations

US (1)