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A Safety Trial of Nivolumab in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Progressed During or After Receiving At Least One Prior Chemotherapy Regimen

Phase 3
Completed
Conditions
Non Small Cell Lung Cancer (NSCLC)
Interventions
Registration Number
NCT02066636
Lead Sponsor
Bristol-Myers Squibb
Brief Summary

The purpose of this study is to estimate the incidence and characterize the outcome of high grade, select adverse events in subjects with advanced or metastatic NSCLC treated with Nivolumab.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1428
Inclusion Criteria
  1. Target Population
  • Subjects with histologically-or cytologically-documented NSCLC [squamous (SQ) or nonsquamous (NSQ)] who present with Stage IIIB/Stage IV disease (according to version 7 of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology), or with recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection or definitive chemoradiotherapy for locally advanced disease)
  • Subjects must have experienced disease progression or recurrence during or after at least one systemic therapy for advanced or metastatic disease
  • Each subsequent line of therapy must be preceded by disease progression. A switch of an agent within a regimen in order to manage toxicity does not define the start of a new line of therapy
  • Maintenance therapy following platinum doublet-based chemotherapy is not considered as a separate regimen of therapy
  • Subjects who received platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, and developed recurrent (local or metastatic) disease within 6 months of completing therapy are eligible
  • Subjects with recurrent disease >6 months after platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, who also subsequently progressed during or after a platinum doublet-based regimen given to treat the recurrence are eligible
  • Subjects with non-squamous histology must be tested for Epithelial Growth Factor Receptor (EGFR) mutations (including, but not limited to, deletions in exon 19 and exon 21 [L858R] substitution) and Anaplastic Lymphoma Kinase (ALK) rearrangement if tests have not been previously performed. Subjects with progressive disease during or after EGFR or ALK tyrosine kinase inhibitor (TKI) regimens are eligible. Subjects are eligible if genetic test results are indeterminate or if no tumor tissue is available or accessible for testing as long as they have received one prior systemic therapy
  • Experimental therapies when given as separate regimen are considered as separate line of therapy
  • Subjects must have measurable disease by CT or MRI per RECIST 1.1 criteria (radiographic tumor assessment performed within 28 days of first dose of study drug) or clinically apparent disease that the investigator can follow for response per RECIST 1.1
  • Eastern Cooperative Oncology Arm (ECOG) performance status (PS)
  • PS 0 to 1
  • PS 2
Exclusion Criteria
  1. Target Disease Exceptions

    • Subjects with active central nervous system (CNS) metastases are excluded
    • Subjects with carcinomatous meningitis
  2. Medical History and Concurrent Diseases

    • Subjects with a history of interstitial lung disease
    • Subjects with active, known or suspected autoimmune disease
    • Subject whom participated in either arm of the following clinical trials CA209-017, CA209-057, CA209-026, and CA184-104 or received prior treatment with anti-programmed death 1 (PD-1) or anti-programmed death-ligand 1 (PDL1) experimental agents
  3. Prohibited Treatments and/or Restricted Therapies

    • Ongoing or planned administration of anti-cancer therapies other than those specified in this study
    • Use of corticosteroids or other immunosuppressive medications

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cohort A: NivolumabNivolumabNivolumab 3 mg/kg solution intravenous infusion over 30 minutes every two weeks until disease progression, unacceptable toxicity, or withdrawal of informed consent
Cohort B: NivolumabNivolumabNivolumab 3 mg/kg solution intravenous infusion over 30 minutes every two weeks until 1 year (52 weeks). Discontinue treatment and at progression, retreatment allowed
Primary Outcome Measures
NameTimeMethod
The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5)From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months)

A treatment related adverse event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that has a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.

Secondary Outcome Measures
NameTimeMethod
Median Time to Onset of Select Adverse Events (Grade 3-5)From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months)

The time from first dose to the first occurrence of any select adverse event of interest. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.

The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse EventsFrom first dose first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months)

The duration of time participants received medication meant to trigger an immune response for any select Adverse events of interest. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.

Median Time to Resolution of Select Adverse Events (Grade 3-5)From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months)

The time from the onset of any select adverse event of interest to its resolution or stabilization. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.

The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse EventsFrom first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months)

The number of participants receiving medication meant to trigger an immune response for any select Adverse events of interest. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.

The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse EventsFrom first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months)

The number of participants receiving \> 40mg prednisone equivalents for any select adverse event of interest. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.

The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse EventsFrom first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months)

An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.

Trial Locations

Locations (118)

Comprehensive Blood And Cancer Center

🇺🇸

Bakersfield, California, United States

Ucla Hema/Onc-Santa Monica

🇺🇸

Los Angeles, California, United States

Central Georgia Cancer Care, Pc

🇺🇸

Macon, Georgia, United States

Local Institution - 0015

🇺🇸

Skokie, Illinois, United States

West KY Hematology Oncology Group PSC

🇺🇸

Paducah, Kentucky, United States

Maryland Oncology Hematology, P.A.

🇺🇸

Columbia, Maryland, United States

North Mississippi Hematology And Oncology Associates, Ltd

🇺🇸

Tupelo, Mississippi, United States

Moses Cone Regional Cancer Center

🇺🇸

Greensboro, North Carolina, United States

Mid Dakota Clinic, Pc

🇺🇸

Bismarck, North Dakota, United States

University Of Illinois Cancer Center

🇺🇸

Chicago, Illinois, United States

Zangmeister Cancer Center

🇺🇸

Columbus, Ohio, United States

Lancaster General Hospital

🇺🇸

Lancaster, Pennsylvania, United States

Indiana University Health Melvin And Bren Simon Cancer Center

🇺🇸

Indianapolis, Indiana, United States

Northwest Cancer Center

🇺🇸

Houston, Texas, United States

Local Institution - 0038

🇺🇸

Miami, Florida, United States

Comprehensive Cancer Center Of Nevada

🇺🇸

Las Vegas, Nevada, United States

Oncology Hematology Care, Incorporated

🇺🇸

Cincinnati, Ohio, United States

Central Coast Med Oncology

🇺🇸

Santa Maria, California, United States

Saint Jude Heritage Medical Group Virginia K Crosson Cancer Center

🇺🇸

Fullerton, California, United States

Sutter Cancer Center

🇺🇸

Sacramento, California, United States

Diablo Valley Oncology

🇺🇸

Concord, California, United States

Piedmont Hospital

🇺🇸

Atlanta, Georgia, United States

Providence Cancer Center

🇺🇸

Southfield, Michigan, United States

Pacific Cancer Care

🇺🇸

Monterey, California, United States

Cancer Center Of Kansas

🇺🇸

Wichita, Kansas, United States

Local Institution

🇨🇦

Montreal, Quebec, Canada

Cancer Center Treatment Center of America

🇺🇸

Goodyear, Arizona, United States

Oncology Specialists

🇺🇸

Park Ridge, Illinois, United States

Torrance Memorial Medical Center

🇺🇸

Torrance, California, United States

Mountain Blue Cancer Care Center

🇺🇸

Golden, Colorado, United States

Southern Cancer Center Pc

🇺🇸

Mobile, Alabama, United States

Greater Baltimore Medical Center

🇺🇸

Baltimore, Maryland, United States

Jackson Oncology Associates, Pllc

🇺🇸

Jackson, Mississippi, United States

Charleston Hematology Oncology Associates, Pa

🇺🇸

Charleston, South Carolina, United States

Greenville Health System

🇺🇸

Greenville, South Carolina, United States

Local Institution - 0031

🇺🇸

Lakeland, Florida, United States

St. Mary Medical Center

🇺🇸

Langhorne, Pennsylvania, United States

Holy Cross Hospital Inc.

🇺🇸

Fort Lauderdale, Florida, United States

Lehigh Valley Hospital

🇺🇸

Allentown, Pennsylvania, United States

Allegheny General Hospital

🇺🇸

Pittsburgh, Pennsylvania, United States

South Carolina Oncology Associates

🇺🇸

Columbia, South Carolina, United States

St. Luke's University Hospital Bethlehem

🇺🇸

Bethlehem, Pennsylvania, United States

Texas Oncology - Odessa

🇺🇸

Midland, Texas, United States

The West Clinic, P.C.

🇺🇸

Germantown, Tennessee, United States

Texas Oncology-Beaumont

🇺🇸

Beaumont, Texas, United States

Texas Oncology-Abilene

🇺🇸

Abilene, Texas, United States

Tennessee Oncology, PLLC - SCRI - PPDS

🇺🇸

Chattanooga, Tennessee, United States

Tennessee Oncology, Pllc

🇺🇸

Nashville, Tennessee, United States

Henry-Joyce Cancer Center

🇺🇸

Nashville, Tennessee, United States

Cancer Care Centers Of South Texas

🇺🇸

San Antonio, Texas, United States

Utah Cancer Specialists

🇺🇸

Salt Lake City, Utah, United States

Huntsman Cancer Institute

🇺🇸

Salt Lake City, Utah, United States

Rocky Mountain Cancer Centers

🇺🇸

Denver, Colorado, United States

Walter Reed National Mltry Medical Center

🇺🇸

Bethesda, Maryland, United States

Nebraska Cancer Specialists

🇺🇸

Omaha, Nebraska, United States

Cancer Care Of Wnc

🇺🇸

Germantown, Tennessee, United States

Local Institution - 0067

🇺🇸

Dallas, Texas, United States

Texas Oncology-Plano East

🇺🇸

Plano, Texas, United States

University Of Virginia Health System.

🇺🇸

Charlottesville, Virginia, United States

Arizona Oncology Associates

🇺🇸

Sedona, Arizona, United States

Arizona Oncol Assoc Dba (Hem Onc Physicians&Extenders) Hope

🇺🇸

Tucson, Arizona, United States

Sansum Santa Barbara Medical Foundation Clinic

🇺🇸

Santa Barbara, California, United States

St. Mary's Hospital Regional Cancer Center

🇺🇸

Grand Junction, Colorado, United States

Eastern Ct Hem Onc Assoc

🇺🇸

Norwich, Connecticut, United States

Florida Cancer Specialists S.

🇺🇸

Fort Myers, Florida, United States

Baptist Cancer Institute

🇺🇸

Jacksonville, Florida, United States

Cancer Institute Of Florida

🇺🇸

Orlando, Florida, United States

Ocala Oncology Center

🇺🇸

Ocala, Florida, United States

Memorial Cancer Institute

🇺🇸

Pemroke Pines, Florida, United States

Local Institution - 0071

🇺🇸

Pensacola, Florida, United States

Hematology/Oncology Associates Of The Treasure Coast

🇺🇸

Port Saint Lucie, Florida, United States

Florida Cancer Specialists

🇺🇸

Saint Petersburg, Florida, United States

Local Institution - 0108

🇺🇸

Tampa, Florida, United States

Space Coast Cancer Center

🇺🇸

Titusville, Florida, United States

University Cancer Blood Ctr

🇺🇸

Athens, Georgia, United States

Cancer Treatment Centers Of America

🇺🇸

Newnan, Georgia, United States

Summit Cancer Care

🇺🇸

Savannah, Georgia, United States

Lewis Hall Singletary Oncology Center

🇺🇸

Thomasville, Georgia, United States

Pearlman Cancer Center

🇺🇸

Valdosta, Georgia, United States

Illinois Cancer Specialists

🇺🇸

Niles, Illinois, United States

Quincy Medical Group

🇺🇸

Quincy, Illinois, United States

Southern Illinois University School Of Medicine

🇺🇸

Springfield, Illinois, United States

Local Institution - 0081

🇺🇸

Fort Wayne, Indiana, United States

Norton Cancer Center

🇺🇸

Louisville, Kentucky, United States

University Medical Center, Inc

🇺🇸

Louisville, Kentucky, United States

Christus Schumpert Health

🇺🇸

Shreveport, Louisiana, United States

Anne Arundel Medical Center

🇺🇸

Annapolis, Maryland, United States

Michigan Cancer Research Consortinum

🇺🇸

Ann Arbor, Michigan, United States

Bay Hematology Oncology

🇺🇸

Easton, Maryland, United States

Cancer & Hematology Centers Of Western Michigan

🇺🇸

Grand Rapids, Michigan, United States

Forrest General Cancer Center

🇺🇸

Hattiesburg, Mississippi, United States

University Of Kansas Cancer Center

🇺🇸

North Kansas City, Missouri, United States

Mercy Medical Research Institute

🇺🇸

Springfield, Missouri, United States

Southeast Nebraska Hematology & Oncology Consultants, P.C.

🇺🇸

Lincoln, Nebraska, United States

VA Sierra Nevada Health Care System

🇺🇸

Reno, Nevada, United States

Atlantic Health System

🇺🇸

Summit, New Jersey, United States

Hunterdon Medical Center

🇺🇸

Flemington, New Jersey, United States

Presbyterian Medical Group

🇺🇸

Albuquerque, New Mexico, United States

Queens Medical Associates

🇺🇸

Fresh Meadows, New York, United States

Maimonides Medical Center

🇺🇸

Brooklyn, New York, United States

Mount Kisco Medical Group

🇺🇸

Mount Kisco, New York, United States

St. Peters Hospital

🇺🇸

Albany, New York, United States

Winthrop University Hospital

🇺🇸

Mineola, New York, United States

Broome Oncology

🇺🇸

Johnson City, New York, United States

Southeastern Medical Oncology Center

🇺🇸

Goldsboro, North Carolina, United States

Columbia University Medical Center (Cumc)

🇺🇸

New York, New York, United States

East Carolina University Leo W. Jenkins Cancer Center

🇺🇸

Greeville, North Carolina, United States

Hematology-Oncology Associates Of Rockland

🇺🇸

Nyack, New York, United States

Randolph Cancer Center

🇺🇸

Asheboro, North Carolina, United States

W.G. Bill Hefner VA Medical Center

🇺🇸

Salisbury, North Carolina, United States

The Jones Clinic, PC

🇺🇸

Germantown, Tennessee, United States

Texas Oncology - Amarillo

🇺🇸

Amarillo, Texas, United States

Texas Oncology

🇺🇸

Mesquite, Texas, United States

The Center For Cancer And Blood Disorders

🇺🇸

Fort Worth, Texas, United States

Texas Oncology Cancer Care And Research Center

🇺🇸

Waco, Texas, United States

Texas Cancer Center - Sherman

🇺🇸

Sherman, Texas, United States

Shenandoah Oncology

🇺🇸

Winchester, Virginia, United States

Kingston General Hospital

🇨🇦

Kingston, Ontario, Canada

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