Clinical trial NCT00401778: Trial of RAD001 in Patients With Operable Non-Small Cell Lung Cancer (NSCLC)
Official title: Trial of RAD001 in Patients With Operable Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lung Cancer
Keywords: Lung Cancer
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2006-11-22
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1b pre-operative lung cancer trial wherein patients with operable lung cancer will be treated with RAD001 to evaluate the target effects of this compounds on relevant molecular pathways and on the 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (FDG) uptake of the tumor by a positron emission tomography (PET) scan at baseline and immediately prior to surgery. The safety profile of RAD001 will also be evaluated.

Detailed description: This is a Phase 1b pre-operative lung cancer trial wherein patients with operable lung cancer will be treated with RAD001 for 3-4 weeks to study the effects of the novel agent in relevant molecular pathways. The study will also assess the FDG uptake of the tumor at baseline and upon completion of therapy (before surgery) with a PET scan. The safety profile of RAD001 will also be evaluated.

New agents and regimens are urgently needed for lung cancer treatment. With the development of novel agents and small molecules designed to curtail the aggressive aspects of this disease, some progress has been realized. However, much more effort and insight will be required for further real gains to be made. We propose that studying the mammalian target of rapamycin (mTOR) axis, known to be abnormal in non-small cell lung cancer (NSCLC), and translating that knowledge into therapeutic adjustments can lead to meaningful advances in lung cancer treatment.

Approximately 35 patients will participate at Winship Cancer Institute of Emory University in Atlanta, Georgia.

Eligibility criteria: Inclusion Criteria:

* Patient must have histologically confirmed Stage I-IIIA non-small cell lung cancer (NSCLC) which is accessible to biopsy.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
* Life-expectancy greater than 6 months.
* Adequate bone marrow, renal, hepatic, pulmonary and cardiac function as defined in the protocol.
* Patient must be at least 18 years of age.
* Must meet pre-entry requirements for timing of study parameters as specified in section 7.0.
* Female patients of child-bearing potential must have a negative serum pregnancy test within 48 hours of study initiation and be non-lactating.
* Patients of child-bearing potential must agree to use an effective form of contraception while on study and for 3 months following completion of study treatment.
* The use of granulocyte-colony stimulating factor (G-CSF) will be permitted in study participants.
* Final eligibility for a clinical trial is determined by the health professionals conducting the trial.

Exclusion Criteria:

* Patient has received previous treatment for NSCLC.
* Known hypersensitivity to everolimus, sirolimus, or any of its excipients.
* Patient is pregnant or breast-feeding.
* Patient has incurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Patient is unable to swallow RAD001 tablet.
* History of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of the malignancy being present within the past five years.
* History of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80. Symptoms may include any reaction such as bronchospasm, generalized urticaria, systolic BP ≤ 80mm Hg, and angioedema.
* Final eligibility for a clinical trial is determined by the health professionals conducting the trial.

Primary outcomes:
measure: Clinical Response as Assessed Metabolically by Changes in Positron Emission Tomography (PET) Scan Between Baseline and Immediately Prior to Surgery.
timeFrame: Day 21
measure: Effects of RAD001 on the Regulation of Key Proteins Involved With the Mammalian Target of Rapamycin (mTOR) Axis in Tumor Specimens and Buccal Mucosa in Patients With Operable Non-small Cell Lung Cancer (NSCLC).
timeFrame: 6 months
measure: Inhibition of Proliferation (Ki67) and Induction of Apoptosis (TUNEL Assay) in Tumor Specimens and Buccal Mucosa.
timeFrame: 6 months
Secondary outcomes:
measure: Safety and Tolerability of RAD001 as Pre-operative Therapy.
timeFrame: 6 months
measure: Duration of Hospital Stay Following Surgery.
timeFrame: 6 months
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Winship Cancer Institute
state: Georgia
Study officials:
affiliation: Emory University Winship Cancer Institute
name: Suresh Ramalingam, MD
role: PRINCIPAL_INVESTIGATOR
References: