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

NCT00892801 | Terminated Phase 1 DMC

• 4 other identifiers: VICC THO 0772P30CA068485VU-VICC-THO-0772IRB#090314
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Lung Cancer; Metastatic Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose

  Safety is measured by the rate of ≥ grade 3 hematological and non-hematologic study-related toxicities.

  4 week DLT period

• Median survival (phase II)

  Off-study date.

Secondary Outcomes (3)

• Intracranial response rate (phase II)

  Off-treatment date.

• Time to CNS (neurologic) progression (phase II)

  Off-treatment date.

• Time to systemic non-CNS progression (phase II)

  Off-treatment date

Study Arms (1)

Treatment

EXPERIMENTAL

RAD001 + radiation therapy

Drug: RAD001; Radiation: whole-brain radiation therapy

Interventions

RAD001 DRUG

Taken by mouth once a day, for 15 days, one day prior to initiation of whole brain radiation therapy 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

Treatment

whole-brain radiation therapy RADIATION

Standard whole brain radiation therapy (WBRT) 30 Gy will be given in ten fractions.

Treatment

Eligibility Criteria

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

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

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

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Vanderbilt-Ingram Cancer Center - Cool Springs

Nashville, Tennessee, 37064, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

MeSH Terms

Conditions

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

Interventions

Everolimus

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; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Vicki Keedy, MD

  Vanderbilt-Ingram Cancer Center

  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: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director, Vanderbilt-Ingram Cancer Center, Clinical Trials Shared Resource; Assistant Professor, Medical Oncologist

Study Record Dates

• First Submitted: May 2, 2009
• First Posted: May 5, 2009
• Study Start: May 1, 2009
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: March 12, 2012

Record last verified: 2012-03

Locations

US (2)