Pirfenidone, Carboplatin, and Paclitaxel or Pemetrexed Disodium in Treating Patients with Stage IIIB-IV Non-small Cell Lung Cancer That Cannot Be Removed by Surgery

Inclusion Criteria

• Histologically/cytologically documented stage IIIB to stage IV unresectable non-small cell lung cancer (either squamous cell carcinoma or non-squamous cell lung cancer or mixed histology; EGFR or ALK mutation excluded unless previously treated with a TKI, given a 2 week washout period) * Patients with adenocarcinoma must have been tested for EGFR and ALK mutations
• At least one measurable tumor lesion as defined by Response Evaluation Criteria in Solid Tumors (Response Evaluation Criteria in Solid Tumors [RECIST]) version (v)1.1 criteria
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Patients should be chemotherapy naive in the stage IV non-small cell lung cancer (NSCLC) setting, with the exception of chemotherapy for neoadjuvant or adjuvant treatment that completed at least 6 months before the study treatment
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
• Platelets >= 100 x 10^9/L
• Hemoglobin level >= 9 g/dL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x upper limit of normal (ULN) or =< 5 X ULN for patients with liver metastases
• Serum creatinine =< 1.5 x ULN or estimated glomerular filtration rate (GFR) >= 50 mL/min/m^2
• Total bilirubin =< 1.5 x ULN
• Urine pregnancy test is negative for women of childbearing potential, within 14 days before study treatment
• Estimated life expectancy of at least 6 months
• Patients may have received prior immunotherapy
• Have archived tissue available or be willing to undergo a fresh biopsy during screening, if deemed feasible by the investigator/study principle investigator (PI); if neither available, the patients enrollment must be reviewed and approved by the PI
• Patients willing to comply with the clinical trial protocol
• Patients voluntarily participate in the clinical trial, understanding they may withdraw participation at any time
• Patients are able to understand and provide written informed consent prior to trial participation

Exclusion Criteria

• Patients who are currently undergoing other anti-tumor therapies or have concurrent active cancer
• Patients who were enrolled into any other treatment clinical trial and received treatment on that trial within 4 weeks of study treatment
• Any clinical laboratory findings give reasonable suspicion of a disease or condition that contraindicates the use of any study medication or render the subject at high risk from treatment
• Patients with previously untreated brain metastases should be excluded; patients with treated and stable (> 4 weeks) brain metastases may be eligible for enrollment
• History of allergic reactions to carboplatin or paclitaxel
• Patients who have had immunotherapy or radiotherapy within 4 weeks prior to study treatment or those who have not recovered from adverse events due to agents administered more than 4 weeks prior to study treatment; prior history of palliative radiation for symptomatic bony or brain metastases is permissible
• Patients who are receiving any other investigational agents
• Patients with known ROS1 mutations who have not received prior targeted therapy
• Alcohol or drug dependence
• Uncontrolled coagulopathy
• Uncontrolled hyper- or hypothyroidism
• Known hypersensitivity to pirfenidone, carboplatin, pemetrexed or paclitaxel
• Pre-existing peripheral neuropathy of grade II or higher
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association [NYHA] class III/IV), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients receiving any medications or substances that are moderate to strong inhibitors CYP1A2 are ineligible
• Pregnant women are excluded from this study because carboplatin and paclitaxel are agents with the potential for teratogenic or abortifacient effects; the effects of pirfenidone on the developing human fetus are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of study drug administration