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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

Trial Status: Active

This randomized phase I / Ib trial studies the side effects and best dose of pirfenidone and how well it works when given together with carboplatin and paclitaxel or pemetrexed disodium in treating patients with stage IIIB-IV non-small lung cancer that cannot be removed by surgery. Pirfenidone may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin, paclitaxel or pemetrexed disodium, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pirfenidone with carboplatin and paclitaxel or pemetrexed disodium may work better in treating patients with non-small cell lung cancer.

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

Florida

Tampa
Moffitt Cancer Center
Status: ACTIVE
Contact: Jhanelle E. Gray
Phone: 813-745-6895

PRIMARY OBJECTIVES:

I. To determine the recommended phase II dose (R2PD) and maximum tolerated dose (MTD) of pirfenidone plus carboplatin and paclitaxel chemotherapy in patients with advanced/metastatic squamous cell lung cancer (SQCLC). (Phase I, SQCLC)

II. To evaluate the clinical efficacy as measured by the overall response rate (ORR) of pirfenidone plus carboplatin and paclitaxel chemotherapy in patients with advanced/metastatic SQCLC. (Phase Ib, SQCLC)

III. To determine the recommended phase II dose (R2PD) and MTD of pirfenidone plus carboplatin and pemetrexed disodium (pemetrexed) chemotherapy in patients with advanced/metastatic non-SQCLC. (Phase I, non-SQCLC)

IV. To evaluate the clinical efficacy as measured by the ORR of pirfenidone plus carboplatin and pemetrexed chemotherapy in patients with advanced/metastatic non-SQCLC. (Phase Ib, non-SQCLC)

SECONDARY OBJECTIVES:

I. To evaluate the early efficacy outcomes including objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) as well as toxicity of patients treated with this investigational combination. (Phase Ib)

II. Pharmacokinetic assessments of pirfenidone.

III. Pharmacodynamic tissue assessments to evaluate the tumor microenvironment.

OUTLINE: This is a phase I, dose-escalation study of pirfenidone followed by a phase Ib study. Patients are randomized to 1 of 2 arms.

ARM I: Patents receive pirfenidone orally (PO) thrice daily (TID) on days 1-21, carboplatin intravenously (IV) over 30 minutes on day 1, and paclitaxel IV on day 1. Treatment repeats every 21 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive pirfenidone PO TID on days 1-21, carboplatin IV over 30 minutes on day 1, and pemetrexed disodium IV over 10 minutes on day 1. Treatment repeats every 21 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Moffitt Cancer Center

Principal Investigator
Jhanelle E. Gray

  • Primary ID MCC-19082
  • Secondary IDs NCI-2017-01810
  • Clinicaltrials.gov ID NCT03177291