Phase 1b Trial of RAD001 in Patients With Operable Non-Small Cell Lung Cancer (NSCLC)

• Determine clinical response as assessed metabolically by changes in PET scan between baseline and immediately prior to surgery. [ Time Frame: Day 21 ] [ Designated as safety issue: No ]
• Determine the effects of RAD001 on the regulation of key proteins involved with the mTOR axis in tumor specimens and buccal mucosa in patients with operable non-small cell lung cancer (NSCLC). [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
• Determine the effects of RAD001 on the inhibition of proliferation (Ki67) and induction of apoptosis (TUNEL assay) in tumor specimens and buccal mucosa from this patient population. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

• Determine clinical response as assessed metabolically by changes in PET scan (50% reduction in SUV) between baseline and immediately prior to surgery.
• Determine the effects of RAD001 on the regulation of key proteins involved with the mTOR axis in tumor specimens and buccal mucosa in patients with operable non-small cell lung cancer (NSCLC).
• Determine the effects of RAD001 on the inhibition of proliferation (Ki67) and induction of apoptosis (TUNEL assay) in tumor specimens and buccal mucosa from this patient population.

• To determine the safety and tolerability of RAD001 as pre-operative therapy in this patient population. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
• To determine if pre-operative treatment with RAD001 affects duration of hospital stay following surgery. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

• To determine the safety and tolerability of RAD001 as pre-operative therapy in this patient population.
• To evaluate the effect of RAD001 on progression free survival (PFS) and overall survival (OS) following surgery and chemotherapy and determine if an association exists between clinical outcomes and p70S6K activation.
• To determine if pre-operative treatment with RAD001 affects duration of hospital stay following surgery.

This is a Phase 1b randomized, 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 FDG uptake of the tumor by a PET scan at baseline and immediately prior to surgery. The safety profile of RAD001 will also be evaluated.

This is a Phase 1b randomized, 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 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.

• Active Comparator: 1
  RAD001 5 mg/day for 21 days sequentially.
  Intervention: Drug: RAD001
• Active Comparator: 3
  RAD001 10 mg/day for 21 days sequentially.
  Intervention: Drug: RAD001

Inclusion Criteria:

• Patient must have histologically confirmed Stage I-IIIA non-small cell lung cancer (NSCLC) which is accessible to biopsy.
• 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 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.