Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Neoadjuvant Nivolumab, or Nivolumab in Combination With Ipilimumab, in Resectable NSCLC (NA_00092076)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02259621
Recruitment Status : Recruiting
First Posted : October 8, 2014
Last Update Posted : June 25, 2019
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:
The proposed study will evaluate the safety and feasibility of preoperative administration nivolumab +/- ipilimumab in patients with high-risk resectable NSCLC, and will facilitate a comprehensive exploratory characterization of the tumor immune milieu and circulating immune cells and soluble factors in these patients. Data obtained in this study will provide valuable information for planning further prospective clinical trials of anti-PD-1 and other immunotherapies in NSCLC, both in the peri-operative and advanced disease setting.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: Nivolumab Phase 2

Detailed Description:

The proposed study will evaluate the safety and feasibility of preoperative administration nivolumab +/- ipilimumab in patients with high-risk resectable NSCLC, and will facilitate a comprehensive exploratory characterization of the tumor immune milieu and circulating immune cells and soluble factors in these patients. Data obtained in this study will provide valuable information for planning further prospective clinical trials of anti-PD-1 and other immunotherapies in NSCLC, both in the peri-operative and advanced disease setting. Ultimately, it is highly desirable to discover prospective biomarkers of response and toxicity to allow patients with NSCLC who are most likely to derive benefit to receive anti-PD-1 treatment, and conversely to minimize the risk of toxicity and ineffective treatment for patients who are unlikely to benefit.

In addition, an amendment to this study allows evaluation of the combination of nivolumab and the anti-CTLA4 antibody, ipilimumab in the neoadjuvant setting for the treatment of resectable NSCLC. In a large, multicohort, phase 1 trial, the ORR to combination ipilimumab and nivolumab therapy in patients unselected by PD-L1 status ranged from 39-47%. Incidence of grade 3-4 toxicity ranged from 33-37% across the combination ipilimumab and nivolumab cohorts which compares favorably with the rates of toxicity due to platinum doublet chemotherapy in this disease setting.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Neoadjuvant Nivolumab, or Nivolumab in Combination With Ipilimumab, in Resectable Non-Small-Cell Lung Cancer.
Study Start Date : September 2014
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : January 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Nivolumab

Nivolumab administration:

Three doses of nivolumab will be administered to enrolled patients on Day -42, Day -28, and Day-14 (+/- two days) prior to planned surgery on Day 0 or up to +10 days.

Drug: Nivolumab
Anti-PD-1 Therapy
Other Name: BMS-936558 or MDX1106




Primary Outcome Measures :
  1. Safety as measured by number of participants with Grade 3 and 4 lab abnormalities, as defined by CTCAE v4.03 [ Time Frame: 8 weeks ]
    Safety will be measured by drawing safety labs. (CBC and a Chemistry Panel will be drawn at 2 week intervals during Nivolumab administration). Grade 3 and 4 lab abnormalities will be recorded from both participating sites.

  2. Safety as assessed by number of Grade 3 and 4 adverse events [ Time Frame: 8 weeks ]
    Number of Grade 3 and 4 adverse events as defined by CTCAE v4.03 that occur while a subject is participating in the study.


Secondary Outcome Measures :
  1. Feasibility as measured by rate of enrollment [ Time Frame: 8 weeks ]
    Rate of enrollment of subjects at all study sites will be measured as average number of participants enrolled at both sites per day.

  2. Pathologic Response [ Time Frame: 6 weeks ]
    Pathologic response to neoadjuvant nivolumab and nivolumab plus ipilimumab in resected tumor and lymph nodes. The rate of major pathologic response, defined as <10% residual viable tumor cells in the resection specimen will be compared to historic data with neoadjuvant chemotherapy.

  3. Radiographic Response [ Time Frame: 5 weeks ]
    Radiographic response to neoadjuvant nivolumab and nivolumab plus ipilimumab as defined by RECIST 1.1.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically proven non-small-cell lung cancer (core biopsy required).

    • Squamous or non-squamous histology
    • Diagnostic core biopsy specimens must be reviewed by a faculty pathologist at SKCCC or MSKCC
    • Either a formalin fixed paraffin block or a minimum of fifteen 5-micron tissue sections (slides) of tumor biopsy sample must be available for biomarker evaluation (study pathologist must review for adequacy of sampling). This can be obtained from archived tissues, or from a new biopsy if needed.
  • Stage - High risk NSCLC with resection option for potential cure, as assessed by a faculty surgeon at SKCCC or MSKCC. This may include clinical stage IB (≥4cm), II and IIIA(see Appendix A). Subjects with N3 nodal involvement are not included.

ECOG performance status 0-1

-Adequate organ function as follows:

  • Leukocytes ≥ 2,000/mm3
  • Absolute neutrophil count (ANC) ≥ 1000/mm3
  • Platelet count ≥ 100,000/mm3
  • Hemoglobin ≥ 9 g/dL
  • Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥40 mL/min (if using the Cockcroft-Gault formula below):

Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL

Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL

  • Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
  • AST(SGOT), ALT(SGPT), and alkaline phosphatase ≤ 3 times the upper limit of normal
  • Subjects must have adequate lung function to permit surgical resection determined by pre-enrollment pulmonary function tests to include DLCO

    • The effects of nivolumab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) 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 and for up to 23 weeks after the last dose of nivolumab. 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. Sexually active fertile men must use effective barrier birth control if their partners are WOCBP for up to 31 weeks after the last dose of nivolumab. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within two weeks of registration. Women must not be breastfeeding.
    • Patient understands the study regimen, its requirements, risks and discomforts and is able and willing to sign the informed consent form. Voluntary signed and dated IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines must be obtained before the performance of any protocol related procedures that are not part of normal patient care. Subjects must be competent to report AEs, understand the drug dosing schedule and use of medications to control AEs.

Exclusion Criteria:

  • Subjects are excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
  • Subjects are excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen.
  • Administration of chemotherapy or any other cancer therapy in the pre-operative period.
  • Subjects with active concurrent malignancies are excluded i.e. cancers other than NSCLC (except non melanoma skin cancers, in situ bladder, gastric, breast, colon or cervical cancers/dysplasia).
  • Subjects with brain metastasis are excluded from this study, and all patients should have brain imaging (either MRI brain or CT brain with contrast) prior to enrollment.
  • Subjects with a history of symptomatic interstitial lung disease.
  • Active systemic infection requiring therapy, positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA).
  • Known positive history or positive test for Human Immunodeficiency Virus or Acquired ImmunoDeficiency Syndrome (AIDS).
  • History of allergy to study drug components.
  • Women who are pregnant or nursing.
  • Men with female partners (WOCBP) that are not willing to use contraception.
  • Prior therapy with an anti-PD-1, anti-PD-L1, anti-PDL-2, or anti-CTLA-4 antibody (or any other antibody targeting T cell co-regulatory pathways).
  • Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events.
  • Prisoners or subjects who are involuntarily incarcerated or compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness.

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): NCT02259621


Contacts
Layout table for location contacts
Contact: Patrick Forde, MD 410-955-8893 pforde1@jhmi.edu
Contact: Heather Schneider, BS 410-502-0984 hschne12@jhmi.edu

Locations
Layout table for location information
United States, District of Columbia
Sibley Memorial Hospital Not yet recruiting
Washington, District of Columbia, United States, 20016
Contact: Benjamin Levy, MD    202-660-6500    blevy11@jhmi.edu   
Contact: Caitlin Joffe         
Principal Investigator: Benjamin Levy, MD         
Sub-Investigator: Bruce Kressel, MD         
Sub-Investigator: Catherine Bishop, MD         
United States, Maryland
Johns Hopkins at Bayview Medical Center Recruiting
Baltimore, Maryland, United States, 21224
Contact: Julie Brahmer, MD    410-502-7159    brahmju@jhmi.edu   
Principal Investigator: Patrick Forde, MD         
Sub-Investigator: Julie Brahmer, MD         
Sub-Investigator: David Ettinger, MD         
Sub-Investigator: Christine Hann, MD         
Sub-Investigator: Valsamo Anagnostou, MD         
Sub-Investigator: Jarushka Naidoo, MD         
Sub-Investigator: Stephen Yang, MD         
Sub-Investigator: David Feller-Kopman, MD         
Sub-Investigator: Janis Taube, MD         
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21287
Contact: Patrick Forde, MD    410-502-7683    pforde1@jhmi.edu   
Sub-Investigator: David S Ettinger, MD         
Sub-Investigator: Christine Hann, MD         
Sub-Investigator: Ronan Kelly, MD         
Sub-Investigator: Julie Brahmer, MD         
Sub-Investigator: Valsamo Anagnostou, MD         
Sub-Investigator: Jarushka Naidoo, MD         
Sub-Investigator: Stephen Yang, MD         
Sub-Investigator: David Feller-Kopman, MD         
Sub-Investigator: Janis Taube, MD         
Principal Investigator: Patrick Forde, MD         
United States, New York
Memorial Sloan Kettering Recruiting
New York, New York, United States, 10065
Contact: Jamie E. Chaft, MD    646-888-4545    chaftj@mskcc.org   
Sub-Investigator: David Jones, MD         
Sub-Investigator: James Isbell, MD         
Sub-Investigator: Matthew Bott, MD         
Canada, Quebec
Johnathan Spicer Not yet recruiting
Montréal, Quebec, Canada, H4 3J1
Contact: Johnathan Spicer, MD    514-934-1934    jonathan.spicer@mcgill.ca   
Contact: Penny Chipman    514-934-1934    mailto:penny.chipman@muhc.mcgill.ca   
Principal Investigator: Johnathan Spicer, MD         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Bristol-Myers Squibb
Investigators
Layout table for investigator information
Principal Investigator: Patrick Forde, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Additional Information:
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT02259621     History of Changes
Other Study ID Numbers: J1414
NA_00092076 ( Other Identifier: JHMIRB )
First Posted: October 8, 2014    Key Record Dates
Last Update Posted: June 25, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents