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Trial record 1 of 2 for:    NCT02768558
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Cisplatin and Etoposide Plus Radiation Followed By Nivolumab/Placebo For Locally Advanced NSCLC

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ClinicalTrials.gov Identifier: NCT02768558
Recruitment Status : Terminated (Another treatment found efficacious)
First Posted : May 11, 2016
Results First Posted : February 25, 2020
Last Update Posted : October 30, 2020
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
RTOG Foundation, Inc.

Brief Summary:
Patients with Stage III unresectable non-small cell lung cancer will receive thoracic radiation, cisplatin and etoposide followed by nivolumab or placebo given every 2 weeks for a year.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Radiation: Radiation Therapy (RT) Drug: Cisplatin Drug: Etoposide Drug: Nivolumab Other: Placebo Phase 3

Detailed Description:

PRIMARY OBJECTIVES:

I. To compare the Overall Survival (OS) for patients with Stage III unresectable non-small cell lung cancer treated with or without nivolumab following concurrent chemoradiation.

II. To compare Progression-Free Survival (PFS) according to RECIST 1.1 criteria for patients with Stage III unresectable non-small cell lung cancer treated with or without nivolumab following concurrent chemoradiation.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Double Blinded Phase III Trial of Cisplatin and Etoposide Plus Thoracic Radiation Therapy Followed By Nivolumab/Placebo For Locally Advanced Non-Small Cell Lung Cancer
Actual Study Start Date : October 17, 2016
Actual Primary Completion Date : January 23, 2019
Actual Study Completion Date : January 23, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Nivolumab
60 Gy of radiation therapy given concurrently with cisplatin-etoposide chemotherapy followed by nivolumab
Radiation: Radiation Therapy (RT)
2 Gy fractions once a day, 5 days per week, for a total of 60 Gy in 30 fractions.
Other Names:
  • 3 Dimensional Conformal Radiation Therapy (3DCRT)
  • Intensity Modulated Radiation Therapy (IMRT)

Drug: Cisplatin
Concurrently with radiation therapy, 50 mg/m2, IV, on days 1, 8, 29, and 36, to begin with day 1 of radiation therapy.
Other Name: Platinol

Drug: Etoposide
Concurrently with radiation, 40 mg/m2, IV, on days 1-5 and 29-33, to begin with day 1 of radiation therapy.
Other Name: VP-16

Drug: Nivolumab
Beginning 4-12 weeks after chemoradiation, 240 mg, IV, every 2 weeks for 16 weeks, then 480 mg, IV, for 36 weeks.
Other Name: Opdivo

Placebo Comparator: Placebo
60 Gy of radiation therapy given concurrently with cisplatin-etoposide chemotherapy followed by placebo
Radiation: Radiation Therapy (RT)
2 Gy fractions once a day, 5 days per week, for a total of 60 Gy in 30 fractions.
Other Names:
  • 3 Dimensional Conformal Radiation Therapy (3DCRT)
  • Intensity Modulated Radiation Therapy (IMRT)

Drug: Cisplatin
Concurrently with radiation therapy, 50 mg/m2, IV, on days 1, 8, 29, and 36, to begin with day 1 of radiation therapy.
Other Name: Platinol

Drug: Etoposide
Concurrently with radiation, 40 mg/m2, IV, on days 1-5 and 29-33, to begin with day 1 of radiation therapy.
Other Name: VP-16

Other: Placebo
Beginning 4-12 weeks after chemoradiation, 240 mg, IV, every 2 weeks for 16 weeks, then 480 mg, IV, for 36 weeks.




Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: From registration to study termination. Maximum follow-up was 14.9 months. ]
    Survival time is defined as time from registration to date of death from any cause and was to be estimated by the Kaplan-Meier method. Given the limited follow-up due to early closure and termination of data collection, only the number of patients last reported to be alive at time of study termination is reported and no statistical testing was done.

  2. Progression-Free Survival (PFS) [ Time Frame: From registration to study termination. Maximum follow-up was 14.9 months. ]

    Progression is defined using the Response Evaluation Criteria In Solid Tumors Criteria (RECIST) guideline v1.1 as a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions at any location. Progression was to be determined by an independent radiology review committee using scans submitted to a central location.

    Progression-free survival time is defined as time from registration to the date of first progression, death, or last known follow-up (censored) and was to be estimated by the Kaplan-Meier method.



Secondary Outcome Measures :
  1. Number of Participants With Grade 3+ Adverse Events [ Time Frame: From registration to study termination. Maximum follow-up was 14.9 months. ]
    Adverse events (AE) are graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.

  2. Percentage of Participants With Deterioration in Functional Assessment of Cancer Therapy - Trial Outcome Index for Lung Cancer (FACT-TOI) at 15 Months [ Time Frame: Baseline and 15 months ]
    FACT-TOI is a measure of 21 items that sum the functional well being (FWB), physical well being (PWB), and the lung cancer subscale (LCS) of the Functional Assessment of Cancer Therapy - Lung (FACT-L) QOL instrument, used for measuring QOL in patients with lung cancer. All items are rated on a 5 item (point) Likert Scale, from 0 (not at all) to 4 (very much). FACT-TOI is scored by summing the individual scale scores, with higher scores indicating better quality of life. Deterioration was defined as a decrease of 5 points or more from baseline.

  3. Overall Survival by PD-L1 Status [ Time Frame: From registration to study termination. Maximum follow-up was 14.9 months. ]
  4. Progression-Free Survival by PD-L1 Status [ Time Frame: From registration to study termination. Maximum follow-up was 14.9 months. ]


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 (histologically or cytologically) proven diagnosis of non-small cell lung cancer (NSCLC) with unresectable, medically inoperable disease, or patients who refuse resection stage IIIA or stage IIIB disease (AJCC 7th edition)
  • History/physical examination within 30 days prior to registration
  • Computed tomography (CT) scan with IV contrast (CT scan without contrast acceptable if IV contrast is medically contraindicated) of the lung and upper abdomen through the adrenal glands within 60 days prior to registration (recommended within 30 days prior to registration)
  • Magnetic resonance imaging (MRI) of the brain with contrast (or CT with contrast if MRI is medically contraindicated) within 60 days prior to registration; note: the use of intravenous contrast is required for the MRI or CT (unless medically contra-indicated).
  • Whole-body fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT within 60 days prior to registration; Note: patients do not need to have a separate CT of chest and upper abdomen with contrast if PET/CT imaging includes a high quality CT chest with contrast.
  • Age ≥ 18 years
  • The trial is open to both genders
  • Zubrod Performance status of 0-1
  • Forced Expiratory Volume at one second (FEV1) > 1.2 liters; Diffusion Capacity of Lung for Carbon Monoxide (DLCO) ≥ 50% predicted
  • Patients must be at least 3 weeks from prior thoracotomy (if performed); if prior thoracotomy then measurable disease on imaging must be present
  • Negative serum pregnancy test within three days prior to registration for women of childbearing potential
  • An archived tumor block or punches instead block must be available for submission for programmed death-ligand 1 (PD-L1) analysis. If an archived tumor block sample cannot be shipped for this study, then two 3mm punches from the core needle biopsy blocks may be provided for analysis. Note: core or excisional biopsy is required for this study. Fine needle aspirates (FNA) and cytology specimens are not adequate for PD-L1 analysis.
  • Agreement of women of childbearing potential to use highly effective contraception during receipt of study drug and up to 161 days (23 weeks) from the last dose of nivolumab/placebo and men receiving nivolumab/placebo who are sexually active with women of childbearing potential to use highly effective contraception during receipt of study drug for 31 weeks from the last dose of nivolumab/placebo.

Exclusion Criteria:

  • Definitive clinical or radiological evidence of metastatic disease
  • Prior or current invasive malignancy (except non-melanomatous skin cancer, localized bladder and prostate cancer) unless disease free for a minimum of 2 years (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields. For example, patients with prior breast radiotherapy treatments would likely be excluded.
  • Prior systemic treatment with and anti-programmed cell death protein 1 (PD1), anti-PD-L1, anti-PD-L2, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) (antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways
  • Known immunosuppressive disease, for example HIV infection or history of bone marrow transplant or chronic lymphocytic leukemia (CLL)
  • Chronic Obstructive Pulmonary Disease (COPD) exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration. COPD requiring chronic oral steroid therapy
  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
  • Transmural myocardial infarction within the last 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  • History of symptomatic or p previously established interstitial lung disease
  • Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection;
  • History of severe hypersensitivity reaction to any monoclonal antibody or allergy to study drug components
  • As there is potential for hepatic toxicity with nivolumab, drugs with a predisposition to hepatotoxicity should be used with caution in patients treated with nivolumab-containing regimen
  • Pregnancy, nursing females or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.

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): NCT02768558


Locations
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United States, California
UC San Diego Moores Cancer Center
La Jolla, California, United States, 92093
Stanford University
Stanford, California, United States, 94305
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
Mount Sinai Cancer Research Center
Miami Beach, Florida, United States, 33140
United States, Georgia
Nancy N. & J.C. Lewis Cancer & Research Pavilion at St. Joseph's/Candler Hospital
Savannah, Georgia, United States, 31405
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, Maryland
Mercy Medical Cancer Center
Baltimore, Maryland, United States, 21202
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
University of Rochester
Rochester, New York, United States, 14642
United States, Ohio
Metro Health Medical Center
Cleveland, Ohio, United States, 44109
United States, Pennsylvania
Reading Hospital/McGlinn Cancer Institute
West Reading, Pennsylvania, United States, 19611
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
United States, Virginia
Inova Fairfax Hospital
Falls Church, Virginia, United States, 22042
United States, Washington
Virginia Mason
Seattle, Washington, United States, 98101
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
RTOG Foundation, Inc.
Bristol-Myers Squibb
Investigators
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Principal Investigator: David Gerber, MD RTOG Foundation
  Study Documents (Full-Text)

Documents provided by RTOG Foundation, Inc.:
Informed Consent Form  [PDF] January 30, 2017

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: RTOG Foundation, Inc.
ClinicalTrials.gov Identifier: NCT02768558    
Other Study ID Numbers: RTOG 3505
RF 3505 ( Other Identifier: RTOG Foundation )
CA209-333 ( Other Identifier: Bristol-Myers Squibb )
First Posted: May 11, 2016    Key Record Dates
Results First Posted: February 25, 2020
Last Update Posted: October 30, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by RTOG Foundation, Inc.:
Lung Cancer
NSCLC
Nivolumab
Additional relevant MeSH terms:
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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
Etoposide
Nivolumab
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological