Hydroxychloroquine + Carboplatin, Paclitaxel and Bevacizumb in Non-Small Cell Lung Cancer (NSCLC)

Inclusion Criteria:

• Signed a protocol-specific informed consent.
• 18 years of age or older.
• ECOG Performance Status 0 or 1.
• Histologically or cytologically confirmed non-small cell lung cancer EXCEPT squamous cell carcinoma. 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 IIIB with malignant pleural effusion, or stage IV, or recurrent disease).
• Measurable disease according to RECIST criteria.
• No known CNS metastases. A head CT or brain MRI is required within 28 days of enrollment.
• No prior cytotoxic chemotherapy or targeted therapy in the advanced or metastatic setting. Post-operative adjuvant therapy for previously resected NSCLC is allowed as long as the last dose was given greater than 1 year before study entry, and there is current evidence of disease progression.
• Prior radiation to sites other than the brain is allowed, if completed at least 2 weeks prior to treatment and provided that all radiation-related toxicities have resolved to ≤ Grade 1.
• No active malignancy other than NSCLC. Patients with a history of basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, or ductal or lobular carcinoma in situ of the breast within the past 3 years must have been treated with curative intent. Patients with a history of prior malignancy are eligible provided they were treated with curative intent and have been free of disease for > 3 years.
• Adequate organ function
• 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 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. Placement of vascular access device is not considered major surgery, but the incision must have healed before initiation of treatment.
• 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 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).
• Patients must not have unstable angina or NYHA classification of congestive heart failure of Grade ≥ 2 (see Appendix C).
• No history of significant vascular disease (eg aortic aneurysm).
• Patients must not have psoriasis or porphyria.
• No known hypersensitivity to 4-aminoquinoline compound.
• Patients must not have retinal or visual field changes from prior 4-aminoquinoline compound use.
• Patients must not have known G-6P deficiency.
• No current or recent (within 28 days of enrollment) full dose anticoagulants or thrombolytic agents.
• No know bleeding diathesis or coagulopathy.
• No known GI pathology that would interfere with drug bioavailability.
• No peripheral or sensory neuropathy > Grade 1 at study entry.
• No known prior hypersensitivity to carboplatin, paclitaxel, bevacizumab or hydroxychloroquine or any of their components.
• No ongoing or active infection at study entry.
• Patients must not be receiving treatment for rheumatoid arthritis or systemic lupus erythematosus.
• Patients must not have HIV or be taking HAART therapy.
• Patients must not have a history of any condition (social or medical) that, in the opinion of the Investigator, might interfere with the patient's ability to comply with the protocol or pose additional or unacceptable risk to the patient.
• Women must NOT be pregnant or breastfeeding.

• Women must :

  • Have a negative serum or urine pregnancy test within 7 days prior to study entry if she is a woman of child-bearing potential
  • Be at least one year post-menopausal
  • Be surgically sterile
• Patients of childbearing or child fathering potential must be willing to use an acceptable method of birth control prior to study entry and for the duration of the study. Acceptable methods of contraception include hormonal, barrier methods, intrauterine device, tubal ligation/vasectomy or abstinence.
• Must not be taking hydroxychloroquine for treatment or prophylaxis of malaria.