QOL-Stereotactic RadioSurgery, Temozolomide + Erlotinib-Rx of 1-3 Brain Metastases in NSCLC

Phase II Quality of Life Study of Stereotactic RadioSurgery, Temozolomide and Erlotinib Chemotherapy for the Treatment of 1-3 Brain Metastases in Non-small Cell Lung Cancer

RATIONALE: Treatment with radiosurgery, temozolomide, and erlotinib may affect brain function (the ability to think, learn, remember, and judge) in patients with non-small cell lung cancer and brain metastases. A study that evaluates brain function may help doctors plan the best treatment.

PURPOSE: This phase II trial is studying the effect of radiosurgery, temozolomide, and erlotinib on brain function in patients with non-small cell lung cancer and brain metastases.

Study Overview

• Status: Withdrawn
• Conditions: Lung Cancer; Metastatic Cancer
• Intervention / Treatment: Drug: erlotinib hydrochloride; Drug: temozolomide; Radiation: stereotactic radiosurgery

Detailed Description

OBJECTIVES:

Primary

• Determine the effect of stereotactic radiosurgery, temozolomide, and erlotinib hydrochloride on cognitive function in patients with non-small cell lung cancer and brain metastases.

Secondary

• Determine the feasibility and safety of this regimen, in terms of tumor response, time to tumor progression in brain, survival, physical functioning, and quality of life, in these patients.
• Determine the frequency of O6-methylguanine-DNA methyltransferase promoter methylation in these patients.

OUTLINE: This is a multicenter study.

Patients undergo stereotactic radiosurgery on day -7. Patients receive oral temozolomide once daily on days 1-5 and oral erlotinib hydrochloride once daily on days 1-23. Treatment with temozolomide and erlotinib hydrochloride repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo cognitive function evaluation as measured by Mini-Mental Status Exam administration and scoring; quality of life assessment as measured by Functional Assessment of Cancer Therapy subscale; and physical functioning assessment as measured by Katz index of activities of daily living and Karnofsky performance status at baseline and then every 8 weeks during study treatment.

Tumor tissue is examined by O6-methylguanine-DNA methyltransferase (MGMT gene) promotor methylation.

After completion of study therapy, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.

• Study Type: Interventional
• Phase: Phase 2

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

DISEASE CHARACTERISTICS:

• Histologically confirmed non-small cell lung cancer meeting the following criteria:

  • One to 3 brain metastases, meeting the following criteria:

    • No larger than 3 cm
    • Greater than 5 mm from the optic apparatus
    • Not involving the brainstem, pons, medulla, or midbrain

  • Stable systemic disease for the past 3 months

    • Less than 3 months since completion of primary treatment
• Measurable CNS disease as defined by RECIST criteria
• No leptomeningeal disease documented by MRI or cerebrospinal fluid cytologic evaluation

PATIENT CHARACTERISTICS:

• Life expectancy ≥ 12 weeks
• Karnofsky performance status 60-100%
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 10 g/dL
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST ≤ 3.0 times ULN
• Serum creatinine ≤ 1.5 mg/dL
• Creatinine clearance > 50 mL/min
• No other malignancy within the past 5 years, except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No concurrent major medical illness or psychiatric impairment that, in the investigator's opinion, would preclude study participation
• No concurrent active infections
• No known HIV positivity
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective nonhormonal contraception during and for 3 months after completion of study treatment

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior complete resection of all brain metastases
• No prior brain radiation therapy
• No prior temozolomide or erlotinib hydrochloride
• No concurrent enzyme-inducing anti-epileptic drugs
• No concurrent recombinant interleukin-11
• No other concurrent anticancer investigational or commercial agents or therapies, including chemotherapy, immunotherapy, hormonal cancer therapy, radiation therapy, or cancer surgery
• No concurrent enrollment on another clinical trial
• Surgery for symptomatic brain lesions prior to radiosurgery allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cognitive function	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Survival	2 years
Tumor response	2 years
Time to tumor progression in brain	2 years
Quality of life as measured by FACT subscale	2 years
Physical functioning as measured by Karnofsky performance status and Katz index of activities of daily living	2 years
Frequency of O6-methylguanine-DNA methyltransferase promoter methylation	2 years

Collaborators and Investigators

• Sponsor: University of Medicine and Dentistry of New Jersey
• Collaborators: National Cancer Institute (NCI); Genentech, Inc.; Schering-Plough
• Investigators: Principal Investigator: Molly Gabel, MD, Rutgers Cancer Institute of New Jersey

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: October 5, 2006
• First Submitted That Met QC Criteria: October 6, 2006
• First Posted (Estimate): October 9, 2006

Study Record Updates

• Last Update Posted (Estimate): September 2, 2013
• Last Update Submitted That Met QC Criteria: August 29, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: stage IV non-small cell lung cancer; tumors metastatic to brain
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Lung Neoplasms; 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: 030601; P30CA072720 (U.S. NIH Grant/Contract); 0220060108 (Other Identifier: IRB Number); CINJ-NJ1506; CDR0000539474