Pirfenidone Combined With Standard First-Line Chemotherapy in Advanced-Stage Lung NSCLC

NCT03177291 | Completed Phase 1 FDA Drug

• 1 other identifier: MCC-19082
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out what effects (good and/or bad) Pirfenidone combined with standard first-line chemotherapy will have on you and non-small cell lung cancer (NSCLC). The investigational drug Pirfenidone is being combined with standard chemotherapy in participants with advanced non-small cell lung cancer. Pirfenidone is approved to treat idiopathic pulmonary fibrosis (IPF) but it isn't currently approved to treat non-small cell lung cancer.

Conditions

Lung Cancer; Non Small Cell Lung Cancer; Advanced Cancer; Metastatic Lung Cancer; Squamous Cell Lung Cancer; Non-Squamous Non-Small Cell Neoplasm of Lung

Keywords

NSCLC; SCLC

Outcome Measures

Primary Outcomes (2)

• Phase 1: Recommended Phase 1b Dose

  Recommended Phase 1b dose of Pirfenidone in combination with standard first-line chemotherapy, based on Dose Limiting Toxicity (DLT) from phase 1. Dose-limiting Toxicity: The occurrence of any of the following toxicities will be considered a DLT, if judged by the Investigator to be possibly, probably, or definitely related to study drug administration, referring to grade 3-5 adverse events as listed in the protocol document.

  6 months post final enrollment in phase 1 - up to 48 months

• Phase 1b: Overall Response Rate (ORR)

  ORR according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1: Complete Response (CR) plus Partial Response (PR). Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm (\<1 cm). Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  6 months post final enrollment in phase 1b - up to 48 months

Secondary Outcomes (2)

• Progression Free Survival (PFS)

  Up to 48 months

• Overall Survival (OS)

  Up to 48 months

Study Arms (2)

Squamous Cell Lung Cancer (SQCLC)

ACTIVE COMPARATOR

Arm A Combination Therapy: Pirfenidone combined with standard first-line chemotherapy. Participants will receive the combination of Pirfenidone and carboplatin plus paclitaxel in study treatment cycles that last 21 days. Phase 1 Dose Escalation; followed by Phase 1b Dose Expansion.

Drug: Pirfenidone; Drug: Carboplatin; Drug: Paclitaxel

Non-Squamous Cell Lung Cancer (SQCLC)

ACTIVE COMPARATOR

Arm B Combination Therapy: Pirfenidone combined with standard first-line chemotherapy. Participants will receive the combination of Pirfenidone and carboplatin plus pemetrexed in study treatment cycles that last 21 days. Phase 1 Dose Escalation; followed by Phase 1b Dose Expansion.

Drug: Pirfenidone; Drug: Carboplatin; Drug: Pemetrexed

Interventions

Pirfenidone DRUG

Pirfenidone: 267 mg Capsules by mouth (PO) 3 times per day (TID). Dose Escalation: Level 1:One capsule (total daily dose 801 mg); Level 2: Two capsules (total daily dose 1602 mg); Level 3: Three capsules (total daily dose 2403 mg). Dose Expansion: Treatment at dose determined by the Phase 1 Dose Escalation.

Also known as: 5-methyl-1-phenyl-1H-pyridine-one, Esbriet

Non-Squamous Cell Lung Cancer (SQCLC); Squamous Cell Lung Cancer (SQCLC)

Carboplatin DRUG

Area under the curve (AUC) 6 on Day 1 of a 21-day cycle for 4 - 6 cycles.

Also known as: Paraplatin

Non-Squamous Cell Lung Cancer (SQCLC); Squamous Cell Lung Cancer (SQCLC)

Paclitaxel DRUG

200 mg/m\^2 on Day 1 of a 21-day cycle for 4 - 6 cycles.

Also known as: Abraxane

Squamous Cell Lung Cancer (SQCLC)

Pemetrexed DRUG

500 mg/m\^2 on Day 1 of a 21-day cycle for 4 - 6 cycles.

Also known as: Alimta

Non-Squamous Cell Lung Cancer (SQCLC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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; epidermal growth factor (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 (RECIST) v1.1.
• years of age and older.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Participants should be chemotherapy naïve in the Stage IV NSCLC setting, with the exception of chemotherapy for neoadjuvant or adjuvant treatment that completed at least 6 months before the study treatment.
• Participants' blood test must meet the following requirements: Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L; Platelets ≥ 100 x 10\^9/L; Hemoglobin level ≥ 9 g/dL.
• Clinical biochemistry examination must meet the following requirements: 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 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.
• 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 PI. If neither available, the patients enrollment must be reviewed and approved by the PI.
• Voluntarily participate in the clinical trial, understanding they may withdraw participation at any time.
• Able to understand and provide written informed consent prior to trial participation.

You may not qualify if:

• 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.
• 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.
• 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 (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.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

pirfenidone; Carboplatin; Paclitaxel; Albumin-Bound Paclitaxel; Pemetrexed

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Study Officials

• Jhanelle Gray, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2017
• First Posted: June 6, 2017
• Study Start: September 26, 2017
• Primary Completion: May 9, 2021
• Study Completion: December 4, 2024
• Last Updated: December 5, 2025

Record last verified: 2025-12

Locations

US (1)