Clinical trial NCT02768558: Cisplatin and Etoposide Plus Radiation Followed By Nivolumab/Placebo For Locally Advanced NSCLC
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer
Keywords: Lung Cancer
NSCLC
Nivolumab
Lead sponsor: RTOG Foundation, Inc.
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2016-05-11
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From registration to study termination. Maximum follow-up was 14.9 months.
measure: Progression-Free Survival (PFS)
timeFrame: From registration to study termination. Maximum follow-up was 14.9 months.
Secondary outcomes:
measure: Number of Participants With Grade 3+ Adverse Events
timeFrame: From registration to study termination. Maximum follow-up was 14.9 months.
measure: Percentage of Participants With Deterioration in Functional Assessment of Cancer Therapy - Trial Outcome Index for Lung Cancer (FACT-TOI) at 15 Months
timeFrame: Baseline and 15 months
measure: Overall Survival by PD-L1 Status
timeFrame: From registration to study termination. Maximum follow-up was 14.9 months.
measure: Progression-Free Survival by PD-L1 Status
timeFrame: From registration to study termination. Maximum follow-up was 14.9 months.
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Cancer Research Center
state: Florida
city: Savannah
country: United States
facility: Nancy N. & J.C. Lewis Cancer & Research Pavilion at St. Joseph's/Candler Hospital
state: Georgia
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: Mercy Medical Cancer Center
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Cleveland
country: United States
facility: Metro Health Medical Center
state: Ohio
city: West Reading
country: United States
facility: Reading Hospital/McGlinn Cancer Institute
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
Study officials:
affiliation: RTOG Foundation
name: David Gerber, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gerber DE, Urbanic JJ, Langer C, Hu C, Chang IF, Lu B, Movsas B, Jeraj R, Curran WJ, Bradley JD. Treatment Design and Rationale for a Randomized Trial of Cisplatin and Etoposide Plus Thoracic Radiotherapy Followed by Nivolumab or Placebo for Locally Advanced Non-Small-Cell Lung Cancer (RTOG 3505). Clin Lung Cancer. 2017 May;18(3):333-339. doi: 10.1016/j.cllc.2016.10.009. Epub 2016 Oct 26.