Clinical trial NCT00385398: QOL-Stereotactic RadioSurgery, Temozolomide + Erlotinib-Rx of 1-3 Brain Metastases in NSCLC
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Lung Cancer
Metastatic Cancer
Keywords: tumors metastatic to brain
stage IV non-small cell lung cancer
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Schering-Plough
name: Genentech, Inc.
First posted: 2006-10-09
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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

Primary outcomes:
measure: Cognitive function
timeFrame: 2 years
Secondary outcomes:
measure: Tumor response
timeFrame: 2 years
measure: Time to tumor progression in brain
timeFrame: 2 years
measure: Survival
timeFrame: 2 years
measure: Quality of life as measured by FACT subscale
timeFrame: 2 years
measure: Physical functioning as measured by Karnofsky performance status and Katz index of activities of daily living
timeFrame: 2 years
measure: Frequency of O6-methylguanine-DNA methyltransferase promoter methylation
timeFrame: 2 years
Other outcomes:
Locations:
Study officials:
affiliation: Rutgers Cancer Institute of New Jersey
name: Molly Gabel, MD
role: PRINCIPAL_INVESTIGATOR
References: