Cisplatin/Carboplatin and Etoposide With or Without Nivolumab in Treating Patients With Extensive Stage Small Cell Lung Cancer
Condition: Extensive Stage Lung Small Cell Carcinoma; Recurrent Lung Small Cell Carcinoma
MeSH terms: Carcinoma; Small Cell Lung Carcinoma; Carcinoma, Small Cell
Intervention: Carboplatin; Cisplatin; Etoposide; Nivolumab
Intervention description: Given IV; Given IV; Given IV; Given IV
Intervention MeSH terms: Cisplatin; Carboplatin; Nivolumab; Etoposide; Etoposide phosphate; Podophyllotoxin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 160.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II clinical trial studies whether the addition of nivolumab to
      cisplatin (or carboplatin) and etoposide will improve outcomes when treating patients with
      extensive stage small cell lung cancer. Chemotherapy drugs, such as cisplatin, carboplatin,
      and etoposide, work in different ways to stop the growth of tumor cells, either by killing
      the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy
      with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the
      cancer, and may interfere with the ability of tumor cells to grow and spread. Giving
      cisplatin/carboplatin and etoposide together with nivolumab may work better in treating
      patients with extensive stage small cell lung cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed extensive stage small
             cell lung cancer and must be a candidate for systemic therapy; NOTE: The extensive
             disease SCLC classification for this protocol includes all patients with disease sites
             not defined as limited stage; limited stage disease category includes patients with
             disease restricted to one hemithorax with regional lymph node metastases, including
             hilar, ipsilateral and contralateral mediastinal, and/or ipsilateral supraclavicular
             nodes; extensive disease patients are defined as those patients with extrathoracic
             metastatic disease, malignant pleural effusion, bilateral or contralateral
             supraclavicular adenopathy; patients with locally recurrent SCLC who are not eligible
             for curative intent chemoradiation are eligible

          -  Patients must have measurable disease based on Response Evaluation Criteria in Solid
             Tumors (RECIST) 1.1

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Absolute neutrophil count >= 1,500/mm^3 (must be obtained =< 7 days prior to protocol
             registration)

          -  Platelets >= 100,000/mm^3 (must be obtained =< 7 days prior to protocol registration)

          -  Leukocytes >= 3000/mm^3 (must be obtained =< 7 days prior to protocol registration)

          -  Hemoglobin >= 9 g/dL (must be obtained =< 7 days prior to protocol registration)

          -  Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (except subjects
             with Gilbert syndrome, who can have total bilirubin < 3 mg/dL) (must be obtained =< 7
             days prior to protocol registration)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 X
             institutional upper limit of normal (ULN) (=< 5 X if liver function test [LFT]
             elevations due to known liver metastases) (must be obtained =< 7 days prior to
             protocol registration)

          -  Serum creatinine =< 1.5 x ULN or calculated creatinine clearance > 50 mL/min (using
             the Cockcroft-Gault formula) (must be obtained =< 7 days prior to protocol
             registration)

          -  Patients are eligible if central nervous system (CNS) metastases are adequately
             treated and neurological symptoms have returned to baseline or are controlled for at
             least 2 weeks prior to enrollment; in addition, subjects must be either off
             corticosteroids, or on a stable or decreasing dose of =< 10 mg daily prednisone (or
             equivalent); patients with untreated CNS metastases are eligible if they are not
             symptomatic and the lesions are less than 1 cm in size

          -  Patients cannot have had prior chemotherapy or biologic therapy for extensive stage
             small cell lung cancer for front line treatment; patients receiving prior whole brain
             radiation cannot register within 7 days after completion of radiation, and must have
             resolved adverse events attributed to radiation to =< grade 1; a 1-week washout is
             permitted for palliative radiation (=< 2 weeks of radiotherapy) to non-CNS disease

          -  Patients who have received prior chemoradiation treatment with chemotherapy regimen
             including cisplatin or carboplatin/etoposide for limited-stage SCLC are eligible if
             treated with curative intent at least 6 months since last treatment from diagnosis of
             extensive-stage SCLC

          -  Patients may not be receiving any other investigational agents while on study

          -  Women of childbearing potential (WOCBP) and males who are sexually active with WOCBP
             must use an accepted and effective method of contraception or abstain from sexual
             intercourse for at least one week prior to the start of treatment, and continue for 5
             months after the last dose of protocol treatment for women of childbearing potential
             and 7 months after the last dose of protocol treatment for males who are sexually
             active with WOCBP

          -  No 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);

          -  No prior systemic treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4
             antibody, or any other antibody or drug specifically targeting T-cell costimulation or
             immune checkpoint pathways;

          -  No patients with an active, known or suspected autoimmune disease and neuromuscular
             paraneoplastic syndromes including but not limited to myasthenia gravis, Lambert-Eaton
             myasthenic syndrome, limbic encephalitis, myositis, Guillain-Barre; subjects with type
             I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders
             (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or
             conditions not expected to recur in the absence of an external trigger are permitted
             to enroll

          -  No patients with a condition requiring systemic treatment with either corticosteroids
             (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 7
             days of randomization; inhaled or topical steroids, and adrenal replacement steroid
             doses > 10 mg daily prednisone equivalent, are permitted in the absence of active
             autoimmune disease

          -  No patients with interstitial lung disease that is symptomatic or may interfere with
             the detection or management of suspected drug-related pulmonary toxicity

          -  No history of severe hypersensitivity reaction to any monoclonal antibody or allergy
             to study drug components

        Exclusion Criteria:

          -  Patients must not have history of allergic reactions attributed to compounds of
             similar chemical or biologic composition to nivolumab or other agents used in the
             study

          -  Women must not be pregnant or breast-feeding; because there is an unknown but
             potential risk for adverse events in nursing infants secondary to treatment of the
             mother with the agents used in this study, breastfeeding must be discontinued or the
             subject is not eligible for the study; all females of childbearing potential must have
             a blood test or urine study, with a minimum sensitivity 50 mlU/L or equivalent units
             of human chorionic gonadotropin (HCG), within 14 days prior to registration to rule
             out pregnancy; a female of childbearing potential is any woman, regardless of sexual
             orientation or whether they have undergone tubal ligation, who meets the following
             criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not
             been naturally postmenopausal for at least 24 consecutive months (i.e. has had menses
             at any time in the preceding 24 consecutive months)

          -  Patient must not have leptomeningeal disease

          -  Patients must NOT have uncontrolled intercurrent illness including, but not limited
             to, ongoing or active infection, symptomatic congestive heart failure, unstable angina
             pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations
             that would limit compliance with study requirements

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible

          -  Any positive test for hepatitis B virus or hepatitis C virus indicating acute or
             chronic infection, patients are excluded

          -  Patients are ineligible if they received a live, attenuated vaccine within 4 weeks
             before randomization