Cisplatin and Etoposide Plus Radiation Followed By Nivolumab/Placebo For Locally Advanced NSCLC
Condition: Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Radiation Therapy (RT); Cisplatin; Etoposide; Nivolumab; Placebo
Intervention description: 2 Gy fractions once a day, 5 days per week, for a total of 60 Gy in 30 fractions.; Concurrently with radiation therapy, 50 mg/m2, IV, on days 1, 8, 29, and 36, to begin with day 1 of radiation therapy.; Concurrently with radiation, 40 mg/m2, IV, on days 1-5 and 29-33, to begin with day 1 of radiation therapy.; Beginning 4-12 weeks after chemoradiation, 240 mg, IV, every 2 weeks for 16 weeks, then 480 mg, IV, for 36 weeks.; Beginning 4-12 weeks after chemoradiation, 240 mg, IV, every 2 weeks for 16 weeks, then 480 mg, IV, for 36 weeks.
Intervention MeSH terms: Nivolumab; Etoposide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lung Cancer; NSCLC; Nivolumab

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.
    

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.