BTCRC-LUN16-081: Phase II Study of Consolidation Immunotherapy with Nivolumab and Ipilimumab or Nivolumab alone following Concurrent Chemoradiotherapy for Unresectable Stage IIIA/IIIB Non-small Cell Lung Cancer (NSCLC).
To determine if consolidation therapy with nivolumab plus ipilimumab or nivolumab alone following concurrent chemoradiation improves 18-month progression free survival (PFS) in subjects with inoperable or unresectable stage IIIA or IIIB NSCLC.
1) To determine if consolidation therapy with nivolumab plus ipilimumab or nivolumab alone following concurrent chemoradiation improves time to metastatic disease and overall survival (OS) in subjects with inoperable or unresectable stage IIIA or IIIB NSCLC.
2) hTo assess toxicity and tolerability of consolidation therapy with nivolumab plus ipilimumab or nivolumab alone following concurrent chemoradiation in subjects with inoperable or unresectable stage IIIA or IIIB NSCLC.
Chemotherapy multiple agents systemic
- Rutgers Cancer Institute of New Jersey
- Principal Investigator
- Salma Jabbour M.D.
- Principal Investigator
Subject must meet all of the following applicable inclusion criteria to participate in this study:
- Written informed consent and HIPAA authorization for release of personal health information.
- Age ≥ 18 years at the time of consent.
- ECOG Performance Status of 0 or 1 within 14 days prior to registration.
- Histological or cytological confirmation of NSCLC. A pathology report confirming the diagnosis of NSCLC must be obtained and reviewed by the treating physician prior to registration to study.
- Must have unresectable or inoperable stage IIIA or IIIB disease. Subjects must be considered unresectable or inoperable based on the judgment of the treating physician.
- Subjects may have completed concurrent chemoradiation with a standard chemotherapy regimen (Cisplatin/Etoposide, Carboplatin/Paclitaxel or Cisplatin/Pemetrexed [non-squamous only]) and a dose of radiation ranging from 59.4-66.6 Gy. Subjects must have stable disease or disease response as evidenced on CT or PET scan evaluation. For those eligible, protocol therapy should begin a minimum of 28 days and a maximum 56 days following the completion of chemoradiation OR Subjects may have completed up to 2 cycles of consolidation therapy started within 4 weeks of completion of radiation. After completion of consolidation chemotherapy, subjects must have stable disease or disease response as evidenced by CT or PET scan evaluation. For those eligible, protocol therapy should begin 3-4 weeks after the last cycle of chemotherapy.
- Prior cancer treatment must be completed at least 28 days prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤Grade 1 or baseline.
- Demonstrate adequate organ function, all screening labs to be obtained within 14 days prior to registration:
- Absolute Neutrophil Count (ANC) ≥ 1.5 K/mm^3
- Hemoglobin (Hgb) ≥ 9 g/dL
- Platelets ≥100,000/mcl
- Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤ 1.5 x upper limit of normal (ULN) OR ≥ 60 mL/min for subjects with creatinine levels >1.5 x institutional ULN
- Bilirubin ≤ 1.5 × ULN OR Direct bilirubin of ≤ ULN for subjects with total bilirubin levels of >1.5x ULN
- Aspartate aminotransferase (AST) ≤ 2.5 × ULN
- Alanine aminotransferase (ALT) ≤ 2.5 × ULN
- International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT/INR/PTT is within therapeutic range of intended use of anticoagulants
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to registration. NOTE: Women are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are post-menopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 62 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL.
- Women of childbearing potential must be willing to abstain from heterosexual activity or use an effective method of contraception from the time of informed consent until 23 weeks after treatment discontinuation.
- Men who are sexually active with women of childbearing potential (WOCBP) must use any contraceptive method with a failure rate of less than 1% per year. Men receiving study drug and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product.
- As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.
Subjects meeting any of the criteria below may not participate in the study:
- Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 23 weeks (female) or 31 weeks (male) after the last dose of trial treatment.
- Active central nervous system (CNS) metastases. Subjects must undergo a head computed tomography (CT) scan or brain MRI within 28 days prior to registration for protocol therapy to exclude brain metastases if symptomatic or without prior brain imaging.
- Treatment with any investigational agent within 28 days prior to registration for protocol therapy.
- Prior chemotherapy, adjuvant therapy, or radiotherapy for lung cancer other than standard concurrent chemoradiation or up to 2 cycles of consolidation.
- Prior therapy with a PD-1, PD-L1, PD-L2 or CTLA-4 inhibitor or a lung cancer-specific vaccine therapy.
- Presence of metastatic disease (stage IV NSCLC) is not allowed. Subjects must be evaluated with a CT or PET scan prior to registration for protocol therapy to exclude metastatic disease.
- Active second cancers.
- Evidence of active autoimmune disease requiring systemic treatment within the past 90 days or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study.
- Interstitial lung disease or history of pneumonitis requiring treatment with corticosteroids.
- Diagnosis of immunodeficiency or is receiving chronic systemic corticosteroid therapy or other immunosuppressive therapy (excludes inhaled corticosteroids) within 7 days of first dose of study drug.
- History of psychiatric illness or social situations that would limit compliance with study requirements.
- Clinically active infection as judged by the site investigator (≥ Grade 2 by CTCAE v4).
- History of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the site investigator.
- Has a known history of active TB (Bacillus Tuberculosis).
- Hypersensitivity to nivolumab, ipilimumab, or any of their excipients.
- Has received a live vaccine within 30 days prior to planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site www.clinicaltrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria. For additional information on this trial or other available clinical trials please contact the research nurse.
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