Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been terminated.
(Terminated due to low accrual. Study was closed to accrual prematurely and did not continue on to Phase II.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Vicki Keedy, MD, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:
NCT00892801
First received: May 2, 2009
Last updated: March 9, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Lung Cancer
Metastatic Cancer
Drug: RAD001
Radiation: whole-brain radiation therapy
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of RAD001 and Radiation Therapy in Patients With Brain Metastasis From Non-small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:


Further study details as provided by Vanderbilt-Ingram Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: 4 week DLT period ] [ Designated as safety issue: Yes ]
    Safety is measured by the rate of ≥ grade 3 hematological and non-hematologic study-related toxicities.

  • Median survival (phase II) [ Time Frame: Off-study date. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Intracranial response rate (phase II) [ Time Frame: Off-treatment date. ] [ Designated as safety issue: No ]
  • Time to CNS (neurologic) progression (phase II) [ Time Frame: Off-treatment date. ] [ Designated as safety issue: No ]
  • Time to systemic non-CNS progression (phase II) [ Time Frame: Off-treatment date ] [ Designated as safety issue: No ]

Enrollment: 5
Study Start Date: May 2009
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
RAD001 + radiation therapy
Drug: RAD001
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
Radiation: whole-brain radiation therapy
Standard whole brain radiation therapy (WBRT) 30 Gy will be given in ten fractions.

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00892801

Locations
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
Vanderbilt-Ingram Cancer Center - Cool Springs
Nashville, Tennessee, United States, 37064
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
Investigators
Principal Investigator: Vicki Keedy, MD Vanderbilt-Ingram Cancer Center
  More Information

No publications provided

Responsible Party: Vicki Keedy, MD, Medical Director, Vanderbilt-Ingram Cancer Center, Clinical Trials Shared Resource; Assistant Professor, Medical Oncologist, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier: NCT00892801     History of Changes
Other Study ID Numbers: VICC THO 0772, P30CA068485, VU-VICC-THO-0772, IRB#090314
Study First Received: May 2, 2009
Last Updated: March 9, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt-Ingram Cancer Center:
tumors metastatic to brain
recurrent non-small cell lung cancer
stage IV non-small cell lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasm Metastasis
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Neoplastic Processes
Pathologic Processes
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms

ClinicalTrials.gov processed this record on November 20, 2014