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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

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ClinicalTrials.gov Identifier: NCT03366766
Recruitment Status : Recruiting
First Posted : December 8, 2017
Last Update Posted : February 22, 2019
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Biological: Nivolumab Drug: Cisplatin Drug: Pemetrexed Disodium Drug: Gemcitabine Hydrochloride Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Nivolumab Plus Cisplatin/Pemetrexed or Cisplatin/Gemcitabine as Induction in Resectable Non-Small Cell Lung Cancer
Actual Study Start Date : December 20, 2017
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Cohort I (nivolumab, cisplatin, pemetrexed disodium)
Patients with non-squamous lung cancer receive nivolumab IV over 30 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
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • NIVO
  • Opdivo
  • ONO-4538

Drug: Cisplatin
Given IV
Other Names:
  • (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 Salt

Drug: Pemetrexed Disodium
Given IV
Other Names:
  • Alimta
  • N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt

Experimental: Cohort I (nivolumab, cisplatin, gemcitabine hydrochloride)
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 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.
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • NIVO
  • Opdivo
  • ONO-4538

Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • Hydrochloride
  • Difluorodeoxycytidine Hydrochloride
  • Gemzar




Primary Outcome Measures :
  1. Major pathologic response (mpCR) defined as < 10% viable tumor [ Time Frame: Up to 63 days ]
    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 :
  1. Incidence of adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 [ Time Frame: Up to 6 months ]
    Safety data will be summarized descriptively.

  2. Progression free survival [ Time Frame: At 1 year ]
    The distribution of progression-free survival will be estimated using the Kaplan-Meier method.

  3. Overall survival [ Time Frame: Up to 6 months ]
    The distribution of overall survival will be estimated using the Kaplan-Meier method.

  4. Overall clinical response [ Time Frame: Up to 6 months ]
    Will be summarized by presence of baseline measurable disease.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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) per 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) 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 (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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03366766


Contacts
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Contact: Ralph Zinner, MD 215-503-5098 ralph.zinner@jefferson.edu

Locations
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United States, Pennsylvania
Abington Hospital - Jefferson Health Recruiting
Abington, Pennsylvania, United States, 19001
Contact: Mark Sundemeyer, MD    215-481-2400      
Principal Investigator: Mark Sundemeyer, MD         
Sidney Kimmel Cancer Center at Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Ralph Zinner, MD    215-503-5098    ralph.zinner@jefferson.edu   
Lankenau Institute for Medical Research Not yet recruiting
Wynnewood, Pennsylvania, United States, 19096
Contact: Paul Gilman, MD    484-476-4837      
Principal Investigator: Paul Gilman, MD         
Sponsors and Collaborators
Sidney Kimmel Cancer Center at Thomas Jefferson University
Bristol-Myers Squibb
Investigators
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Principal Investigator: Ralph Zinner, MD Sidney Kimmel Cancer Center at Thomas Jefferson University

Additional Information:
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Responsible Party: Sidney Kimmel Cancer Center at Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT03366766     History of Changes
Other Study ID Numbers: 17P.556
First Posted: December 8, 2017    Key Record Dates
Last Update Posted: February 22, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Carcinoma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Cisplatin
Gemcitabine
Nivolumab
Pemetrexed
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors