Erlotinib With or Without Hydroxychloroquine in Chemo-Naive Advanced NSCLC and (EGFR) Mutations

Inclusion Criteria:

* Pathologically confirmed diagnosis of non-small cell lung cancer
* Stage IV disease by the American Joint Committee on Cancer/IASLC 7th edition proposed edition staging criteria
* An EGFR sensitizing mutation must be detected in tumor tissue. Specifically, patients harboring the most common mutations, deletions in exon 19 or the L858R mutation in exon 21 are eligible. Presence of the known resistance mutation T790M as detected by direct tumor sequencing is not allowed. Other rare EGFR mutations may be eligible after discussion with the overall principal investigator
* Age equal to or greater than 18 years
* Measurable disease by RECIST criteria, defined as the presence of at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as 10mm or greater with spiral CT scan
* ECOG Performance status of 0, 1 or 2
* Since prior radiation or surgery, 14 days or more must have elapsed before starting protocol treatment
* No prior treatment with erlotinib, gefitinib, or other small molecule EGFR-TKIs. Prior treatment in the adjuvant setting is allowed if at least 1 year has elapsed since TKI course.
* Adequate organ function as outlined in the protocol
* Patients must undergo a screening eye exam to obtain approval for HCQ treatment, which establishes the absence of baseline conditions include macular degeneration, visual field changes, other retinal disease, and cataracts that interfere with required funduscopic examinations
* No G6PD deficiency, as HCQ may cause hemolysis in patients with G6DP

Exclusion Criteria:

* Symptomatic CNS metastases or newly diagnosed CNS metastases that have not yet been definitively treated with radiation and/or surgery. Note that patients with a history of CNS metastases or cord compression are allowed if they have been definitively treated and are clinically stable. Maintenance steroids are allowed but maintenance seizure medication with an EIAED is not allowed
* Prior radiation therapy inclusive of all identified target lesions. Note that prior palliative radiation to bony disease, CNS disease, or a limited thoracic area is allowed, provided that there is measurable disease outside the field and radiation is completed at least two weeks prior to starting treatment and the patient has fully recovered from all side effects
* Current use of hydroxychloroquine for any reason
* Known hypersensitivity to chloroquine, hydroxychloroquine, or any closely related drug: erlotinib, gefitinib, or any closely related drug
* Patients who are pregnant or breastfeeding. Female subjects of childbearing potential and male subjects must practice acceptable methods of birth control
* Any evidence of clinically active interstitial lung disease. Note that patients with chronic, stable radiographic changes who are asymptomatic are eligible
* Invasive malignancies within the past 3 years except for adequately treated carcinoma of the cervix, basal or squamous cell carcinomas of the skin
* Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study, including a prior diagnosis of porphyria or non-light-sensitive psoriasis, as HCQ can significantly exacerbate both of these conditions
* Use of any non-FDA approved or investigational agent in 30 days or less of enrolling onto the trial, or failure to recover from the side effects of any of these agents
* Penicillamine use for Wilson's disease or any other indication, as concomitant use with HCQ can increase toxicity to penicillamine
* Life expectancy of less than 12 weeks