Clinical Trials /

Nivolumab, Cisplatin, and Pemetrexed Disodium or Gemcitabine Hydrochloride in Treating Patients With Stage I-IIIA Non-small Cell Lung Cancer That Can Be Removed by Surgery

NCT03366766

Description:

This phase II trial studies how well Nivolumab, Cisplatin, and Pemetrexed Disodium or Gemcitabine Hydrochloride in treating patients with stage I-IIIA non-small cell lung cancer that can be removed by surgery. Monoclonal antibodies, such as Nivolumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as Cisplatin and Pemetrexed Disodium or Gemcitabine Hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving Nivolumab, Cisplatin, and Pemetrexed Disodium or Gemcitabine Hydrochloride may work better in treating patients with non-small cell lung cancer.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab, Cisplatin, and Pemetrexed Disodium or Gemcitabine Hydrochloride in Treating Patients With Stage I-IIIA Non-small Cell Lung Cancer That Can Be Removed by Surgery
  • Official Title: Nivolumab Plus Cisplatin/Pemetrexed or Cisplatin/Gemcitabine as Induction in Resectable Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: 17P.556
  • NCT ID: NCT03366766

Conditions

  • Non-Squamous Non-Small Cell Lung Carcinoma
  • Stage I Non-Small Cell Lung Cancer
  • Stage IA Non-Small Cell Lung Carcinoma
  • Stage IB Non-Small Cell Lung Carcinoma
  • Stage II Non-Small Cell Lung Cancer
  • Stage IIA Non-Small Cell Lung Carcinoma
  • Stage IIB Non-Small Cell Lung Carcinoma
  • Stage IIIA Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
NivolumabBMS-936558, NIVO, Opdivo, ONO-4538Cohort I (nivolumab, cisplatin, pemetrexed disodium)
Cisplatin(SP-4-2)-Diamminedichloroplatinum, Abiplatin, Blastolem, Briplatin, (CDDP) Cis-diammine-dichloroplatinum, Cis-dichloroammine Platinum (II), Metaplatin, Plastistil, Platinol, Platinex, Platinol-AQ VHA Plus, Peyrone's SaltCohort I (nivolumab, cisplatin, pemetrexed disodium)
Pemetrexed DisodiumAlimta, N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium SaltCohort I (nivolumab, cisplatin, pemetrexed disodium)
Gemcitabine HydrochlorideHydrochloride, Difluorodeoxycytidine Hydrochloride, GemzarCohort I (nivolumab, cisplatin, gemcitabine hydrochloride)

Purpose

This phase II trial studies how well Nivolumab, Cisplatin, and Pemetrexed Disodium or Gemcitabine Hydrochloride in treating patients with stage I-IIIA non-small cell lung cancer that can be removed by surgery. Monoclonal antibodies, such as Nivolumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as Cisplatin and Pemetrexed Disodium or Gemcitabine Hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving Nivolumab, Cisplatin, and Pemetrexed Disodium or Gemcitabine Hydrochloride may work better in treating patients with non-small cell lung cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To estimate major pathologic response (mpCR) in patients with newly diagnosed and
      untreated non-small cell lung cancer (NSCLC) stage I-IIIA treated with three courses of
      induction nivolumab added to either cisplatin/pemetrexed or cisplatin/gemcitabine prior to
      surgery.

      SECONDARY OBJECTIVES:

      I. Safety. II. Complete pathologic response at all sites of disease. III. Major pathologic
      response rate at primary site. IV. Clinical complete response rate. V. 1 year progression
      free survival (PFS). VI. Overall survival.

      TERTIARY OBJECTIVES:

      I. To explore whether PDL1 expression is associated with treatment response. II. To explore
      whether there is a net change in the Th1/Th2 ratio (IFN-gamma, IL-4, IL10, etc.) or cell
      subset frequencies (M2 monocytes, myeloid-derived suppressor cells, etc.) within a patient's
      peripheral blood either at baseline or in response to treatment is associated with treatment
      response.

      III. To explore whether exosomes or other immune related serum biomarkers change after
      combination therapy.

      IV. To explore the predictive value of serial cell free deoxyribonucleic acid (DNA) levels
      and response.

      V. PD-L1 assessment in tumor.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort I (nivolumab, cisplatin, pemetrexed disodium)ExperimentalPatients with non-squamous lung cancer receive nivolumab IV over 60 minutes, cisplatin IV over 60-120 minutes, and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity
  • Cisplatin
  • Pemetrexed Disodium
Cohort I (nivolumab, cisplatin, gemcitabine hydrochloride)ExperimentalPatients with squamous lung cancer receive nivolumab IV over 60 minutes on day 1, cisplatin IV over 60-120 minutes on day 1, and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity.
  • Gemcitabine Hydrochloride

Eligibility Criteria

        Inclusion Criteria:

          -  Pathologically confirmed non small cell lung cancer (NSCLC), not previously treated,
             with a plan to undergo surgery

          -  Stage I-IIIA (stage I tumors must be >= 4 cm)

          -  Tumor sample must be available for PD-L1 testing; archival tissue within 3 months of
             study enrollment will be used; if archival tissue is unavailable, a fresh biopsy will
             be taken

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  While blood cells 2000/ul or more

          -  Absolute neutrophil count 1500/ul or more

          -  Platelets 100,000/ul or more

          -  Hemoglobin 9 g/dl or more; (transfusion permitted)

          -  Bilirubin less than or equal to 1.5 x the upper limit of normal (except subjects with
             Gilbert syndrome, who can have total bilirubin < 3 mg/dl)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal
             to 3 x the upper limit of normal

          -  Glomerular filtration rate (GFR) greater than or equal to 40 ml/min using the
             Cockcroft-Gault formula or serum creatinine less than or equal to 1.5 x (ULN) upper
             limit of normal

          -  Women of reproductive potential should have a negative serum or urine pregnancy test
             (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin
             [HCG]) within 21 days of the study enrollment

          -  Women of reproductive potential must use highly effective contraception methods to
             avoid pregnancy for 23 weeks after the last dose of study drugs; "women of
             reproductive potential" is defined as any female who has experienced menarche and who
             has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or
             who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea
             in a woman over 45 in the absence of other biological or physiological causes; in
             addition, women under the age of 55 must have a documented serum follicle stimulating
             hormone (FSH) level less than 40 mIU/mL

          -  Men of reproductive potential who are sexually active with women of reproductive
             potential must use any contraceptive method with a failure rate of less than 1% per
             year; men who are receiving the study medications will be instructed to adhere to
             contraception for 31 weeks after the last dose of study drugs; men who are azoospermic
             do not require contraception

          -  All subjects must be able to comprehend and sign a written informed consent document

        Exclusion Criteria:

          -  Patients who have participated in a study with an investigational agent or device
             within 2 weeks of enrollment

          -  Any prior radiotherapy to the lung

          -  Any prior treatment for NSCLC

          -  Epidermal growth factor receptor (EGFR) or alkaline phosphatase (ALK) activating
             alteration

          -  Any prior therapy with anti-PD-1, anti-PD-L2, anti-CTLA-4 antibody, or any other
             antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint
             pathways

          -  Any history of a sever hypersensitivity reaction to any monoclonal antibody

          -  Any history of allergy to the study drug components

          -  Any concurrent malignancies- exceptions include- basal cell carcinoma of the skin,
             squamous cell carcinoma of the skin, superficial bladder cancer or in situ cervical
             cancer that has undergone potentially curative therapy; patients with a history of
             other prior malignancy must have been treated with curative intent and must have
             remained disease-free for 3 years post-diagnosis

          -  Any diagnosis of immunodeficiency or receiving systemic steroid therapy or any other
             form of immunosuppressive therapy within 14 days of initiation of therapy

          -  Patients that have an active autoimmune disease requiring systemic treatment within
             the past 3 months or a documented history of clinically severe autoimmune disease, or
             a syndrome that requires systemic steroids (> 10 mg daily prednisone equivalents) or
             immunosuppressive agents; subjects with vitiligo, type I diabetes mellitus, or
             resolved childhood asthma/atopy would be an exception to this rule; subjects that
             require intermittent use of bronchodilators or local steroid injections would not be
             excluded from the study; subjects with hypothyroidism stable on hormone replacement or
             Sjorgen's syndrome will not be excluded from the study

          -  Patients with evidence of interstitial lung disease or active, non-infectious
             pneumonitis. Patients with a history of interstitial lung disease or non-infectious
             pneumonitis requiring treatment with steroids are also excluded.

          -  Patients with a known human immunodeficiency virus infection (HIV 1/2 antibodies) or
             acquired immunodeficiency syndrome (HIV/AIDS), active hepatitis B (e.g., hepatitis B
             surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV]
             ribonucleic acid [RNA] [qualitative] is detected)

          -  Patients who have received a live vaccine within 30 days prior initiation of the
             systemic regimen

          -  Patients must not be receiving any other investigational agents

          -  Patients with uncontrolled intercurrent illnesses including, but not limited to an
             active infection requiring systemic therapy or a known psychiatric or substance abuse
             disorder(s) that would interfere with cooperation with the requirements of the trial

          -  Women must not be pregnant (as above) or breastfeeding
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Major pathologic response (mpCR) defined as < 10% viable tumor
Time Frame:Up to 63 days
Safety Issue:
Description:A minimax Simon two-stage design will be used. The mpCR rate and its associated score 95% confidence interval will be estimated using the methods

Secondary Outcome Measures

Measure:Incidence of adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
Time Frame:Up to 6 months
Safety Issue:
Description:Safety data will be summarized descriptively.
Measure:Progression free survival
Time Frame:At 1 year
Safety Issue:
Description:The distribution of progression-free survival will be estimated using the Kaplan-Meier method.
Measure:Overall survival
Time Frame:Up to 6 months
Safety Issue:
Description:The distribution of overall survival will be estimated using the Kaplan-Meier method.
Measure:Overall clinical response
Time Frame:Up to 6 months
Safety Issue:
Description:Will be summarized by presence of baseline measurable disease.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sidney Kimmel Cancer Center at Thomas Jefferson University

Last Updated

January 3, 2018