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A Phase I/II Study of RAD001 and Radiation Therapy in Patients With Brain Metastasis From Non-small Cell Lung Cancer (NSCLC)

Phase 1
18 Years
Not Enrolling
Lung Cancer, Metastatic Cancer

Thank you

Trial Information

A Phase I/II Study of RAD001 and Radiation Therapy in Patients With Brain Metastasis From Non-small Cell Lung Cancer (NSCLC)

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.



- 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)


- 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.

Inclusion Criteria


- 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


- 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

- 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


- 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

- 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

- 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

- 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

- No other concurrent investigational therapy

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose

Outcome Description:

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

Outcome Time Frame:

4 week DLT period

Safety Issue:


Principal Investigator

Vicki Keedy, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Vanderbilt-Ingram Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

May 2009

Completion Date:

February 2011

Related Keywords:

  • Lung Cancer
  • Metastatic Cancer
  • tumors metastatic to brain
  • recurrent non-small cell lung cancer
  • stage IV non-small cell lung cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms
  • Neoplasm Metastasis
  • Neoplasms
  • Neoplasms, Second Primary



Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
Vanderbilt-Ingram Cancer Center - Cool SpringsNashville, Tennessee  37064