Cisplatin and Etoposide Plus Radiation Followed By Nivolumab/Placebo For Locally Advanced NSCLC

NCT ID: NCT02768558

Last Updated: 2021-06-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-17
• Study Completion Date: 2019-01-23

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.

Conditions

Non-Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Nivolumab

60 Gy of radiation therapy given concurrently with cisplatin-etoposide chemotherapy followed by nivolumab

Group Type: EXPERIMENTAL

Radiation Therapy (RT)

Intervention Type: RADIATION

2 Gy fractions once a day, 5 days per week, for a total of 60 Gy in 30 fractions.

Cisplatin

Intervention Type: DRUG

Concurrently with radiation therapy, 50 mg/m2, IV, on days 1, 8, 29, and 36, to begin with day 1 of radiation therapy.

Etoposide

Intervention Type: DRUG

Concurrently with radiation, 40 mg/m2, IV, on days 1-5 and 29-33, to begin with day 1 of radiation therapy.

Nivolumab

Intervention Type: DRUG

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

Placebo

60 Gy of radiation therapy given concurrently with cisplatin-etoposide chemotherapy followed by placebo

Group Type: PLACEBO_COMPARATOR

Radiation Therapy (RT)

Intervention Type: RADIATION

2 Gy fractions once a day, 5 days per week, for a total of 60 Gy in 30 fractions.

Cisplatin

Intervention Type: DRUG

Concurrently with radiation therapy, 50 mg/m2, IV, on days 1, 8, 29, and 36, to begin with day 1 of radiation therapy.

Etoposide

Intervention Type: DRUG

Concurrently with radiation, 40 mg/m2, IV, on days 1-5 and 29-33, to begin with day 1 of radiation therapy.

Placebo

Intervention Type: OTHER

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

Interventions

Radiation Therapy (RT)

2 Gy fractions once a day, 5 days per week, for a total of 60 Gy in 30 fractions.

Intervention Type: RADIATION

Cisplatin

Concurrently with radiation therapy, 50 mg/m2, IV, on days 1, 8, 29, and 36, to begin with day 1 of radiation therapy.

Intervention Type: DRUG

Etoposide

Concurrently with radiation, 40 mg/m2, IV, on days 1-5 and 29-33, to begin with day 1 of radiation therapy.

Intervention Type: DRUG

Nivolumab

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

Intervention Type: DRUG

Placebo

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

Intervention Type: OTHER

Other Intervention Names

3 Dimensional Conformal Radiation Therapy (3DCRT); Intensity Modulated Radiation Therapy (IMRT); Platinol; VP-16; Opdivo

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

RTOG Foundation, Inc.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Gerber, MD

Role: PRINCIPAL_INVESTIGATOR

RTOG Foundation

Locations

UC San Diego Moores Cancer Center

La Jolla, California, United States

Stanford University

Stanford, California, United States

University of Florida

Gainesville, Florida, United States

Mount Sinai Cancer Research Center

Miami Beach, Florida, United States

Nancy N. & J.C. Lewis Cancer & Research Pavilion at St. Joseph's/Candler Hospital

Savannah, Georgia, United States

University of Kentucky

Lexington, Kentucky, United States

Mercy Medical Cancer Center

Baltimore, Maryland, United States

Henry Ford Health System

Detroit, Michigan, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

University of Rochester

Rochester, New York, United States

Metro Health Medical Center

Cleveland, Ohio, United States

Reading Hospital/McGlinn Cancer Institute

West Reading, Pennsylvania, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Inova Fairfax Hospital

Falls Church, Virginia, United States

Virginia Mason

Seattle, Washington, United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 27923550 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

RF 3505

Identifier Type: OTHER

Identifier Source: secondary_id

CA209-333

Identifier Type: OTHER

Identifier Source: secondary_id

RTOG 3505

Identifier Type: -

Identifier Source: org_study_id