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

Status: Active

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. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and 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.

Eligibility Criteria

Inclusion Criteria

  • Pathologically confirmed NSCLC, not previously treated, with a plan to undergo surgery
  • Stage I-IIIA (stage I tumors must be >= 4 cm) per American Joint Committee on Cancer (AJCC) 8th edition
  • 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
  • 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 more 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
  • EGFR or 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 severe 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 (excludes emergency steroid use at discretion of the treating physician)
  • 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

Locations & Contacts

Pennsylvania

Abington
Abington Memorial Hospital
Status: Active
Contact: Mark L. Sundermeyer
Phone: 215-481-2400
Philadelphia
Thomas Jefferson University Hospital
Status: Active
Contact: Ralph Goldman Zinner
Phone: 215-955-8875
Wynnewood
Lankenau Medical Center
Status: In review
Contact: Paul B. Gilman
Phone: 610-645-2494
Email: gilmanP@MLHS.org

Trial Objectives and Outline

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.

EXPLORATORY 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.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT I: Patients with non-squamous lung cancer receive nivolumab intravenously (IV) over 30 minutes, cisplatin IV over 60-120 minutes, and pemetrexed disodium IV over 10 minutes on day 1. Cycles repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity.

COHORT II: Patients with squamous lung cancer receive nivolumab IV over 30 minutes on day 1, cisplatin IV over 60-120 minutes on day 1, and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Cycles repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 6 months and then periodically thereafter.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Thomas Jefferson University Hospital

Principal Investigator
Ralph Goldman Zinner

Trial IDs

Primary ID 17P.556
Secondary IDs NCI-2017-02198
Clinicaltrials.gov ID NCT03366766