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

University of Medicine and Dentistry of New Jersey

Status and phase

Withdrawn

Phase 2

Conditions

Metastatic Cancer

Lung Cancer

Treatments

Drug: temozolomide

Drug: erlotinib hydrochloride

Radiation: stereotactic radiosurgery

Study type

Interventional

Funder types

Other

Industry

NIH

Identifiers

NCT00385398

P30CA072720 (U.S. NIH Grant/Contract)

CINJ-NJ1506

CDR0000539474

0220060108 (Other Identifier)

030601

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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