Clinical Trial 19082

Cancer Type: Thoracic
Interventions:Alimta (Pemetrexed); Paraplatin (carboplatin); Pemetrexed; Pirfenidone; Taxol (paclitaxel); carboplatin; paclitaxel

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • Jhanelle Gray

Overview

Study Title

A Phase I/Ib Trial of Pirfenidone Combined with Standard First-Line Chemotherapy in Advanced-Stage Lung NSCLC

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.

Objective

SQCLC: The primary objective of the Phase I dose-escalation trial is to determine the recommended Phase II dose (R2PD) and MTD of pirfenidone plus carboplatin and paclitaxel chemotherapy in patients with advanced/metastatic SQCLC. The primary objective of the Phase Ib trial is to evaluate the clinical efficacy as measured by the ORR of pirfenidone plus carboplatin and paclitaxel chemotherapy in patients with advanced/metastatic SQCLC. Non-SQCLC: The primary objective of the Phase I dose-escalation trial is to determine the recommended Phase II dose (R2PD) and MTD of pirfenidone plus carboplatin and pemetrexed chemotherapy in patients with advanced/metastatic non-SQCLC. The primary objective of the Phase Ib trial is to evaluate the clinical efficacy as measured by the ORR of pirfenidone plus carboplatin and pemetrexed chemotherapy in patients with advanced/metastatic non-SQCLC.

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; epidermal growth factor (EGFR) or ALK mutation excluded unless previously treated with a TKI). 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.
  • Males and females18 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) less than or equal to 2.5 x upper limit of normal (ULN) or less than or equal to 5 X ULN for patients with liver metastases; Serum creatinine less than or equal to1.5 x ULN or estimated GFR ≥ 50 mL/min/m^2; Total bilirubin less than or equal to1.5 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.

  • Exclusion Criteria

  • 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.
  • Pregnant women are excluded from this study. Women of child-bearing potential and men must agree to use adequate contraception 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.