Modulation of Autophagy in Patients With Advanced/Recurrent Non-small Cell Lung Cancer - Phase II

Inclusion Criteria

• Signed a protocol-specific informed consent.
• 18 years of age or older.
• ECOG Performance Status 0 or 1.

Cancer criteria:

• Histologically or cytologically confirmed non-small cell lung cancer. Mixed tumors will be categorized by the predominant cell type unless small cell elements are present, in which case the patient is ineligible. Cytologic or histologic elements can be established on metastatic tumor aspirate or biopsy. Sputum cytology alone is not sufficient.
• Advanced stage NSCLC (stage IVa ((malignant pleural effusion (is now staged as stage IVa by the most recent staging system), or stage IV, or recurrent disease)).
• Measurable disease according to RECIST criteria.
• Patient with CNS metastasis are required to have stable disease documented by being off treatment (surgery, or Whole Brain radiation therapy) for at least 2 weeks, and four (4) weeks is preferred. No delay in onset of therapy is required for those patients who undergo stereotactic RT to the brain lesion(s). A contrast enhanced brain CT or brain MRI is required within 35 days of enrollment. Patients with brain metastases who qualify for protocol therapy will be included in Cohort 2 (ineligible for treatment with Bevacizumab).
• Prior radiation to sites other than the brain is allowed, if completed at least 2 weeks before treatment and provided that all radiation-related toxicities have resolved to ≤ Grade 1. Stereotactic irradiation to any site excludes the need for a waiting period.

Laboratory requirements

• Adequate organ function, as evidenced by ALL the following:
• absolute neutrophil count (ANC) ≥ 1500/mm³
• platelet count ≥ 100,000/mm³
• hemoglobin ≥ 9 gm/dL
• total bilirubin ≤ 1.5 x ULN; if patient has Gilbert's disease, then patient must have isolated hyperbilirubinemia (e.g. no other liver function test abnormality), with maximum bilirubin ≤ 2 X institutional ULN.
• AST and ALT ≤ 2.5 x ULN in the absence of liver metastases; AST and ALT ≤ 5 x ULN in the presence of liver metastases
• alkaline phosphatase ≤ 2.5 x ULN
• creatinine ≤ 1.5 X institutional ULN or calculated creatinine clearance ≥ 60 ml/min as estimated using the Cockcroft-Gault formula.

Comorbidities For Cohort 1: (Bevacizumab eligible)

• For patients who have had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment, or anticipate the need for such while on active treatment, may participate and receive Bevacizumab at the start of the second or third cycle as they would under standard care. Placement of vascular access device is not considered major surgery, but the incision must have healed before initiation of treatment.
• Patients must have a systolic blood pressure ≤ 150 mm Hg and diastolic blood pressure ≤ 100 mm Hg (the use of antihypertensive medications to achieve these goals is allowed).
• Adequate organ function
• INR ≤ 1.5 and aPTT WNL.
• Urine Protein Creatinine (UPC) ratio 3 years.

Comorbidities

For Cohort 1: (Bevacizumab eligible)

• No history of gross hemoptysis (defined as bright red blood of a half-teaspoon or more) within 3 months prior to enrollment.
• None of the following conditions within 6 months prior to enrollment: myocardial infarction, stroke or symptomatic peripheral vascular disease.
• No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to enrollment.
• No serious non-healing wound, ulcer or bone fracture.
• Patients must not have unstable angina or NYHA classification of congestive heart failure of Grade ≥ 2.
• No history of significant vascular disease (eg aortic aneurysm).
• No current or recent (within 28 days of enrollment) full dose anticoagulants or thrombolytic agents.

For Cohort 2 (Bevacizumab ineligible):

• None of the following conditions within 6 months prior to enrollment: myocardial infarction, stroke or symptomatic peripheral vascular disease.
• Patients must not have unstable angina or NYHA