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

NCT02768558 | Terminated Phase 3 Results DMC

• 3 other identifiers: RTOG 3505RF 3505CA209-333
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 16

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.

Conditions

Non-Small Cell Lung Cancer

Keywords

Lung Cancer; NSCLC; Nivolumab

Outcome Measures

Primary Outcomes (2)

• Overall Survival (OS)

  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.

  From registration to study termination. Maximum follow-up was 14.9 months.

• Progression-Free Survival (PFS)

  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.

  From registration to study termination. Maximum follow-up was 14.9 months.

Secondary Outcomes (4)

• Number of Participants With Grade 3+ Adverse Events

  From registration to study termination. Maximum follow-up was 14.9 months.

• Percentage of Participants With Deterioration in Functional Assessment of Cancer Therapy - Trial Outcome Index for Lung Cancer (FACT-TOI) at 15 Months

  Baseline and 15 months

• Overall Survival by PD-L1 Status

  From registration to study termination. Maximum follow-up was 14.9 months.

• Progression-Free Survival by PD-L1 Status

  From registration to study termination. Maximum follow-up was 14.9 months.

Study Arms (2)

Nivolumab

EXPERIMENTAL

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

Radiation: Radiation Therapy (RT); Drug: Cisplatin; Drug: Etoposide; Drug: Nivolumab

Placebo

PLACEBO COMPARATOR

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

Radiation: Radiation Therapy (RT); Drug: Cisplatin; Drug: Etoposide; Other: Placebo

Interventions

Radiation Therapy (RT) RADIATION

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

Also known as: 3 Dimensional Conformal Radiation Therapy (3DCRT), Intensity Modulated Radiation Therapy (IMRT)

Nivolumab; Placebo

Cisplatin DRUG

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

Also known as: Platinol

Nivolumab; Placebo

Etoposide DRUG

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

Also known as: VP-16

Nivolumab; Placebo

Nivolumab DRUG

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

Also known as: Opdivo

Nivolumab

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• RTOG Foundation, Inc.: lead
• Bristol-Myers Squibb: collaborator

Study Sites (16)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Mount Sinai Cancer Research Center

Miami Beach, Florida, 33140, United States

Location

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

Savannah, Georgia, 31405, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Mercy Medical Cancer Center

Baltimore, Maryland, 21202, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Metro Health Medical Center

Cleveland, Ohio, 44109, United States

Location

Reading Hospital/McGlinn Cancer Institute

West Reading, Pennsylvania, 19611, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Virginia Mason

Seattle, Washington, 98101, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• 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.

  PMID: 27923550 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Radiotherapy; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Cisplatin; Etoposide; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Radiotherapy, Computer-Assisted; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

This study was terminated early due to the reporting of another study which changed this population's standard of care and rendered the control arm obsolete. Eight of the planned 550 analyzable participants were enrolled at the time of termination.

Results Point of Contact

• Title: Wendy Seiferheld
• Organization: RTOG Foundation

wseiferheld@acr.org

215-574-3208

Study Officials

• David Gerber, MD

  RTOG Foundation

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2016
• First Posted: May 11, 2016
• Study Start: October 17, 2016
• Primary Completion: January 23, 2019
• Study Completion: January 23, 2019
• Last Updated: June 2, 2021
• Results First Posted: February 25, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)