Erlotinib Hydrochloride and Quinacrine Dihydrochloride in Stage IIIB-IV Non-Small Cell Lung Cancer

Inclusion Criteria: * Patients must have histologically or cytologically confirmed incurable malignancy that is surgically unresectable locally advanced, recurrent, or metastatic (stage IIIB/IV) non-small cell lung cancer (NSCLC). Patients with adenocarcinoma, squamous cell carcinoma, large cell carcinoma and sarcomatoid carcinoma will be eligible. * Patients must have received at least one platinum-containing regimen for the treatment of advanced or metastatic disease (except for EGFR-mutant patients). Prior maintenance therapy is allowed and will be considered as the same line of therapy when continued without discontinuation after initiation of a treatment regimen. NSCLC with documented EGFR mutation will be eligible after progression on an EGFR-TKI alone. NSCLC with other molecular targets, such as fusion gene involving the anaplastic lymphoma kinase (ALK) gene (such as echinoderm microtubule associated protein like 4 \[EML4\]-ALK) or ROS-1 will be eligible if they have progressed on targeted agents (ALK inhibitor) and chemotherapy or are not a candidate for chemotherapy. Adjuvant/neoadjuvant chemotherapy or chemoradiation is considered a line of therapy if \< 12 months have elapsed between the last dose and the date of recurrence. Combined treatment with chemotherapy and radiation constitutes a single regimen. * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * Life expectancy of ≥ 12 weeks, in the opinion of and as documented by the investigator * Hemoglobin ≥ 9.0 g/dl (transfusion and/or growth factor support allowed) * Absolute neutrophil count (ANC) ≥ 1,500/mcL * Platelet count ≥ 100 x 10\^9 L * Alkaline phosphatase \< 2.5 X institutional upper limit of normal (in subjects with no liver metastasis and \< 5.0 upper limit of normal \[ULN\] in subjects with liver metastasis) * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 2.5 X institutional upper limit of normal (in subjects with no liver metastasis and \< 5.0 ULN in subjects with liver metastasis) * Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min * Serum total bilirubin ≤ 1.5 x ULN OR total bilirubin ≤ 4.0 ULN with direct bilirubin ≤ 1.5 x ULN in patients with well documented Gilbert syndrome * Patients who are receiving therapeutic anticoagulation with heparin are allowed to participate provided that no prior evidence of underlying abnormality exists in these parameters. Patients on warfarin are eligible provided they are on stable doses of warfarin and there is close monitoring of INR. * Resolution of any toxic effects of prior therapy (including radiotherapy) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0, grade ≤ 1 (with the exception of alopecia and ≤ grade 2 neuropathy); subject must have recovered from significant surgery-related complications * Women of childbearing potential must have a negative pregnancy test performed within 48 hours prior to the start of the study drug * Women of child-bearing potential and men must agree to use adequate contraception (double barrier method of birth control or abstinence) prior to study entry, for the duration of study participation and for 90 days after completing the last investigational drug dose; should a woman become pregnant or suspect that she is pregnant while she or her partner is participating in this study, she should inform the treating physician immediately * Subjects must have the ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: * Patients with previous anti-cancer chemotherapy, immunotherapy or investigational agents ≤ 3 weeks prior to the first day of study defined treatment. NSCLC patients with EGFR mutation can enroll within 7 days of discontinuing EGFR-TKI. Palliative radiation \< 1 week before the start of treatment (lesions subjected to radiotherapy may not be used as target lesions). Patients who receive gamma knife radiosurgery for brain metastases within 1 week prior to treatment start. * Patients with unknown status of EGFR mutation (only for patients with adenocarcinoma histology) * Patients that have had major surgery ≤ 3 weeks or minor surgery (e.g. talc pleurodesis, excisional biopsy, etc) ≤ 1 week prior to the first day of study defined treatment. * History of cardiac disease: congestive heart failure defined as class II to IV per New York Heart Association (NYHA) classification; active coronary artery disease (CAD); previously diagnosed bradycardia or other cardiac arrhythmia defined as ≥ grade 2 according to NCI-CTCAE (version 4.0), or uncontrolled hypertension; myocardial infarction occurred within 6 months prior to study entry (myocardial infarction occurred \> 6 months prior to study entry is permitted) * Patients with clinically unstable central nervous system (CNS) metastasis (to be enrolled in the study, subjects must have confirmation of stable disease by magnetic resonance imaging \[MRI\] or computed tomography \[CT\] scan within 4 weeks of the first day of study defined treatment and have CNS metastases well controlled by steroids, anti-epileptics or other symptom-relieving medications) * Patients with significant gastrointestinal disorder that, in the opinion of the investigator, could interfere with absorption of quinacrine and/or erlotinib (eg, Crohn's disease, small or large bowel resection, malabsorption syndrome) * Patients with any known contraindication to treatment with, including hypersensitivity to quinacrine or erlotinib * Patients with active clinically serious infections defined as ≥ grade 2 according to NCI CTCAE, version 4.0 * Patients with substance abuse, medical, psychological or social conditions that may, in the opinion of the Investigator, interfere with the patient's participation in the study or evaluation of the study results * Any other condition that is unstable or which could jeopardize the safety of the patient and his/her protocol compliance * History of incurable malignancy other than NSCLC within the 5 years prior to start of treatment, with the exceptions of adequately treated intraepithelial carcinoma of the cervix uteri; prostate carcinoma with a prostate-specific antigen value \<0.2 ng/mL; or basal or squamous-cell carcinoma of the skin. * Pregnant or breastfeeding women and adults of reproductive potential not employing an effective method of birth control are excluded from this study because quinacrine is category N agent with the potential for teratogenic or abortifacient effects; these potential risks may also apply to other agents used in this study * Patients with previously known infection with human immunodeficiency virus (HIV) or active viral hepatitis are ineligible because of the potential for pharmacokinetic interactions with quinacrine; (diagnostic testing for these infections will be done only if clinically indicated) * Patients with known Glucose-6-phosphate deficiency, psoriasis, porphyria and psychosis (quinacrine may exacerbate the symptoms of these disorders)