Everolimus and Whole-Brain Radiation Therapy in Treating Patients With Brain Metastasis From Non-Small Cell Lung Cancer

Vanderbilt University Medical Center

Status and phase

Terminated

Phase 1

Conditions

Metastatic Cancer

Lung Cancer

Treatments

Drug: RAD001

Radiation: whole-brain radiation therapy

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00892801

VICC THO 0772

VU-VICC-THO-0772

P30CA068485 (U.S. NIH Grant/Contract)

IRB#090314

Details and patient eligibility

About

RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving everolimus together with whole-brain radiation therapy may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus and to see how well it works when given together with whole-brain radiation therapy in treating patients with brain metastasis from non-small cell lung cancer.

Full description

Phase I is intended to determine the maximum tolerated dose. Study drug will be administered orally, once a day, for 15 days, one day prior to initiation of WBRT at 5 or 10 mg/day during the phase I component. One of these doses will be selected as the maximum tolerable dose and will be selected for the phase II component.

OBJECTIVES:

Primary

To determine the maximum-tolerated dose of everolimus when combined concurrently with whole-brain radiotherapy in patients with brain metastasis from stage IV non-small cell lung cancer. (Phase I)
To evaluate the median survival of these patients treated with this regimen. (Phase II)

Secondary

To assess the response rates in these patients. (Phase II)
To assess the safety and tolerability of this regimen in these patients. (Phase II)
To determine time to CNS (neurological) progression, confirmed by MRI, in these patients. (Phase II)
To determine time to systemic (non-CNS) progression in these patients. (Phase II)

OUTLINE: This is a multicenter, dose-escalation study of everolimus.

Patients undergo 10 fractions of whole-brain radiotherapy (WBRT) beginning on day 0, 5 days per week, and receive oral everolimus once daily on days -1 to 13. Beginning 2 weeks after completion of WBRT, patients receive oral everolimus once daily for 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 2 months for 2 years.

Enrollment

5 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Radiographically confirmed brain metastases with histopathologically confirmed primary non-small cell lung cancer that will benefit from whole-brain radiotherapy
Must have ≥ 1 measurable intracranial site of disease, according to RECIST criteria, that has not been previously treated with stereotactic radiation
Must have stable extracranial disease for 4 weeks

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy ≥ 12 weeks
ANC > 1,500/mm³
Platelets > 100,000/mm³
Hemoglobin > 11 g
BUN ≤ 25 mg
Serum creatinine < 1.5 times upper limit of normal (ULN)
Serum bilirubin ≤ 1.5 times ULN
Serum transaminases ≤ 2 times ULN (< 5 times ULN if patient has liver metastases)
Cholesterol ≤ 300 mg/dL
Triglycerides ≤ 2.5 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
No other malignancies within the past 3 years, except for adequately treated carcinoma in situ of the cervix or basal or squamous cell carcinomas of the skin
No severe and/or uncontrolled medical conditions or other conditions that could affect participation in the study, including any of the following:
- Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within the past 6 months, or serious uncontrolled cardiac arrhythmia
- Severely impaired lung function (i.e., FEV1 < 0.8 cc)
- Uncontrolled diabetes as defined by fasting serum glucose ≥ 1.5 times ULN
- Any active (acute or chronic) or uncontrolled infection/disorders
- Non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy
- Liver disease, such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis
No known history of HIV seropositivity
No impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
No active, bleeding diathesis
No known hypersensitivity to everolimus or other rapamycin (i.e., sirolimus, temsirolimus) or to its excipients
No history of noncompliance to medical regimens

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Recovered from the acute toxicities of any prior therapy
Prior surgical resection of a brain metastasis allowed
- The extent of surgical resection in patients having prior resection of 1 of multiple metastases shall be documented as a biopsy, subtotal resection, or total resection as described by the operative report and/or post-operative imaging
At least 3 weeks since prior major surgery or completion of extracranial radiation
At least 3 weeks since prior and no concurrent systemic anticancer therapy, other than the study medications administered as part of this study protocol
At least 6 weeks since prior nitrosoureas
More than 1 week since prior and no concurrent immunization with attenuated live vaccines
More than 3 weeks since prior chemotherapy
No prior brain radiotherapy of any form
No concurrent chronic treatment with systemic steroids or other immunosuppressive agents, except steroids for neurological stability following the diagnosis of brain metastases
No prior treatment with an mTOR inhibitor
No concurrent anti-vitamin K medication, except low dose coumarin
No concurrent drugs or substances known to be inhibitors or inducers of the isoenzyme CYP3A
No other concurrent investigational therapy