Inclusion Criteria:
- STEP 1 INCLUSION ELIGIBILITY CRITERIA - CONCURRENT THERAPY
- Patient must have one of the following:
- Newly diagnosed stage IIIA/B/C non-small cell lung cancer (NSCLC) (per the
American Joint Committee on Cancer [AJCC] 8th edition) that is unresectable and
is histologically and/or cytologically confirmed
- Nodal recurrence after surgery for early stage NSCLC
- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0
or 1
- Body weight > 30 kg of patients
- Patient must not have unintentional weight loss > 10% within 30 days prior to
registration
- Patient must have a baseline electrocardiography (ECG) obtained within 6 weeks of
registration
- Patient must have measurable disease per Response Evaluation Criteria in Solid Tumors
(RECIST) version (v)1.1. Baseline imaging assessments and measurements used to
evaluate all measurable or non-measurable sites of disease must be done within 4 weeks
prior to registration
- Absolute neutrophil count (ANC) >= 1500 cells/uL (obtained =< 7 days prior to
registration)
- White blood cells (WBC) counts >= 2500/uL (obtained =< 7 days prior to registration)
- Platelet count >= 100,000/uL (obtained =< 7 days prior to registration)
- Hemoglobin >= 9.0 g/dL (obtained =< 7 days prior to registration)
- Total bilirubin =< 1.5 x upper limit of normal (ULN) with the following exception:
patients with known Gilbert disease who have serum bilirubin level < 3 x ULN may be
enrolled (obtained =< 7 days prior to registration)
- Aspartate aminotransferase (AST) and alanine transaminase (ALT) =< 3.0 x ULN (obtained
=< 7 days prior to registration)
- Serum creatinine =< 1.5 x ULN or creatinine clearance >= 45 mL/min on the basis of the
Cockcroft-Gault glomerular filtration rate estimation (obtained =< 7 days prior to
registration)
- Patient must have pulmonary function tests (PFTs) with both forced expiratory volume
in 1 second (FEV1) and diffusion capacity of the lung for carbon monoxide (DLCO) >=
40% of predicted, obtained within 5 months of registration
- Patient is expected to have lung volume (V)20 of =< 35%, after radiation oncologist
views pre-treatment work up
- Patients with nodal recurrence after surgery for early-stage NSCLC are eligible if the
following criteria are met:
- No prior chemotherapy or radiation was ever administered for this lung cancer
originally or for recurrence prior to entering this protocol
- Prior curative-intent surgery was at least 90 days prior to the nodal recurrence
- No prior radiation was administered to the region of study cancer that would
cause overlap of treatment fields
- Patients who are human immunodeficiency virus (HIV) positive may participate in the
study IF they meet all of the following eligibility requirements:
- They must be stable on their anti-retroviral regimen, and they must be healthy
from an HIV perspective
- They must have a CD4 count of greater than 250 cells/mcL, within 6 months of
registration
- They must not be receiving prophylactic therapy for an opportunistic infection
- Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial. Patients must not have had
chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C)
prior to registration
- Patient must not be pregnant or breast-feeding due to the potential harm to an unborn
fetus and possible risk for adverse events in nursing infants with the treatment
regimens being used. Patients must also not expect to conceive or father children from
the time of registration, while on study treatment, and until 90 days after the last
dose of study treatment
- All patients of childbearing potential must have a negative blood test or urine study,
with a minimum sensitivity 50 mlU/L or equivalent units of human chorionic
gonadotropin (HCG), within 7 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
achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral
oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer
therapy does not rule out childbearing potential) for at least 24 consecutive months
(i.e. has had menses at any time in the preceding 24 consecutive months)
- Patients of childbearing potential (WOCBP) and patients who are sexually active with
WOCBP must use accepted and highly effective method(s) of contraception during sexual
intercourse for at least one week prior to the start of treatment, during protocol
treatment, and continue for 90 days after the last dose of protocol treatment
- Highly effective methods of contraception include Etonogestrel-releasing implants
(Implanon or Norplant), Intravaginal: Ethinylestradiol/etonogestrel-releasing
intravaginal devices: e.g., NuvaRing, injection: Medroxyprogesterone injection:
e.g., Depo-Provera, combined pill: Normal and low dose combined oral
contraceptive pill, patch: Norelgestromin/ethinylestradiol-releasing transdermal
system: e.g., Ortho Evra, Minipillc: Progesterone based oral contraceptive pill
using desogestrel: Cerazette is currently the only highly effective progesterone
based pill
- Methods that are considered inadequate include male or female condom with or
without spermicide; female cap, diaphragm, or sponge with or without spermicide;
non-copper containing intrauterine device; progestogen-only oral hormonal
contraceptive pills where inhibition of ovulation is not the primary mode of
action [excluding Cerazette/desogestrel which is considered highly effective];
and triphasic combined oral contraceptive pills)
- STEP 2 INCLUSION ELIGIBILITY CRITERIA - CONSOLIDATION
- Patients with any > grade 2 non-hematologic or > grade 3 hematologic toxicities must
recover to grade 2 (or less) within 45 days after the end of concurrent
chemo/radiation, with the exception of alopecia, vitiligo, and the laboratory values
defined in the inclusion criteria
Exclusion Criteria:
- STEP 1 EXCLUSION ELIGIBILITY CRITERIA - CONCURRENT THERAPY
- Patient must not have any 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-Barré, systemic lupus erythematosus, and systemic sclerosis. Patients with
type I diabetes mellitus requiring insulin, 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 eligible
- Patient must not have a history of active hepatitis B (chronic or acute) or hepatitis
C infection. Patients with past or resolved hepatitis B infection (defined as having a
negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to
hepatitis B core antigen] antibody test) are eligible. Patients positive for hepatitis
C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is
negative for hepatitis C virus ribonucleic acid (HCV RNA)
- Patient must not have a known active tuberculosis infection
- Patient must not have any severe infections within 4 weeks prior to registration
including, but not limited to, hospitalization for complications of infection,
bacteremia, or severe pneumonia
- Patient must not have signs or symptoms of severe infection (sepsis) within 2 weeks
prior registration
- Patient must not have been treated with systemic immunostimulatory agents (including
but not limited to interferon-a [IFN-a], interleukin [IL]-2) within 6 weeks or five
half-lives of the drug (whichever is shorter) prior to registration; or treated with
an investigational agent within 4 weeks prior to registration (or within five
half-lives of the investigational agent, whichever is longer)
- Patient must not have a history of severe allergic, anaphylactic, or other
hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- Patient must not have been treated with systemic immunosuppressive medications
(equivalent to > 10 mg prednisone per day) or other immunosuppressive medications
within 7 days of registration. Inhaled or topical steroids and adrenal replacement
steroid doses equivalent to > 10 mg prednisone per day are permitted in the absence of
active autoimmune disease
- Patient must not have had a prior allogeneic bone marrow transplantation or prior
solid organ transplantation
- Patient must not have a history of idiopathic pulmonary fibrosis, pneumonitis
(including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans,
cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on
screening chest computed tomography (CT) scan within 4 weeks of registration
- Patient must not have had any 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
- Patient with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment and severity
of cardiac symptoms. Symptoms should be stable over the past 3 months. Specifically,
patient must not have coronary artery bypass grafting, myocardial infarction, acute
coronary syndrome severe/unstable angina, stroke, transient ischemic attack, or heart
failure hospitalization within 3 months prior to registration
- Patient must not have an uncontrolled intercurrent illness, including but not limited
to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled
hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease,
serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric
illness/social situations that would limit compliance with study requirement,
substantially increase risk of incurring adverse events (AEs) or compromise the
ability of the patient to give written informed consent
- Patient must not have received a live, attenuated vaccine within 4 weeks prior to
registration
- Patient must not have had past radiation to the current intended treatment site
- Patient must not donate blood while on study treatment
- STEP 2 EXCLUSION ELIGIBILITY CRITERIA - CONSOLIDATION
- Patients must not receive any non-protocol anti-cancer therapy after the end of
chemo/radiation or during consolidation
- Patients with suspected cases of >= grade 2 pneumonitis (non-infectious) are not
eligible for consolidative MEDI4736 (durvalumab) and will proceed onto follow-up
instead
- Patients must not have disease progression on the first post-treatment (for concurrent
chemo/radiation) chest CT scan, which must be obtained within 14 days after the last
dose of radiation therapy. If so, the patient is not eligible for consolidative
MEDI4736 (durvalumab) and will proceed onto follow-up instead
