NCI ID NCI-2019-06124
NCT ID NCT04092283
CTEP ID EA5181
Primary Purpose TREATMENT
Anatomic Sites Lung
Minimum Age 18 Years
Maximum Age 999 Years
Gender BOTH
Lead Org ECOG-ACRIN Cancer Research Group
Principal Investigator Nathan Adam Pennell
NCI Site View on ClinicalTrials.gov

Testing the Addition of an Antibody to Standard Chemoradiation followed by the Antibody for One Year to Standard Chemoradiation followed by One Year of the Antibody in Patients with Unresectable Stage III Non-Small Cell Lung Cancer

This phase III trial studies how well an antibody (durvalumab) with chemotherapy and radiation therapy (chemoradiation) works in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This study is being done to see if adding durvalumab to standard chemoradiation followed by additional durvalumab can extend patients life and/or prevent the tumor from coming back compared to the usual approach of chemoradiation alone followed by durvalumab.

Eligibility

Inclusion Criterea

  • STEP 1 INCLUSION ELIGIBILITY CRITERIA - CONCURRENT THERAPY
  • Patient must be >= 18 years old
  • 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
  • Patient must have a body weight > 30 kg
  • 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 prior to 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 institutional 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 institutional ULN (obtained =< 7 days prior to registration)
  • Serum creatinine =< 1.5 x institutional 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 prior to 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, obtained within 6 months prior to 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.
  • 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 HCG, within 7 days prior to registration to rule out pregnancy. A patient of childbearing potential is anyone, 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 must not expected to conceive or father children by using 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 Step 1 concurrent chemo/radiation, with the exception of alopecia and vitiligo

Exclusion Criterea

  • 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 prior to 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 prior to 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 or sperm while on study treatment
  • STEP 2 EXCLUSION ELIGIBILITY CRITERIA - CONSOLIDATION
  • Patient must not receive any non-protocol anti-cancer therapy after the end of Step 1 chemo/radiation or during Step 2 consolidation
  • Patients with suspected cases of >= grade 2 pneumonitis (non-infectious) are not eligible for Step 2 consolidative MEDI4736 (durvalumab) and will proceed onto follow-up instead
  • Patient must not have disease progression on the first post-treatment (Step 1 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 Step 2 consolidative MEDI4736 (durvalumab) and will proceed onto follow-up instead

Participating Clinics

North Star Lodge Cancer Center at Yakima Valley Memorial Hospital


808 North 39th Avenue
Yakima, WA 98902
Map

509-574-3535
Memorial-ClinicalTrials@yvmh.org

Comprehensive Cancer Centers of Nevada - Central Valley


3730 South Eastern Avenue
Las Vegas, NV 89169
Map

702-384-0013
research@sncrf.org

PCR Oncology


584 Camino Mercado
Arroyo Grande, CA 93420
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada-Southeast Henderson


1505 Wigwam Parkway
Suite 130 Henderson, NV 89074
Map

702-384-0013
research@sncrf.org

Las Vegas Cancer Center-Medical Center


6450 Medical Center Street
Las Vegas, NV 89148-2405
Map

702-384-0013
research@sncrf.org

Las Vegas Cancer Center-Henderson


2904 West Horizon Ridge Parkway
Suite 200 Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Henderson


52 North Pecos Road
Henderson, NV 89074
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Las Vegas


3006 South Maryland Parkway
Suite 100 Las Vegas, NV 89109
Map

702-384-0013
research@sncrf.org

Radiation Oncology Centers of Nevada Southeast


3980 South Eastern Avenue
Las Vegas, NV 89119
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Fort Apache


6160 South Fort Apache Road
Las Vegas, NV 89148
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Vegas Tenaya


2851 North Tenaya Way
Suite 100 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at Fort Apache


6190 South Fort Apache Road
Las Vegas, NV 89148
Map

702-384-0013
research@sncrf.org

HealthCare Partners Medical Group Oncology/Hematology-San Martin


8285 West Arby Avenue
Suite 100 Las Vegas, NV 89113
Map

702-384-0013
research@sncrf.org

HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills


6850 North Durango Drive
Suite 120 Las Vegas, NV 89149
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada-Summerlin


655 North Town Center Drive
Las Vegas, NV 89144
Map

702-384-0013
research@sncrf.org

HealthCare Partners Medical Group Oncology/Hematology-Tenaya


2851 North Tenaya Way
Suite 101 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Henderson


10001 South Eastern Avenue
Suite 108 Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

Carson Tahoe Regional Medical Center


1535 Medical Parkway
Pharmacy Suite C Carson City, NV 89703
Map

702-384-0013
research@sncrf.org

University Cancer Center


3131 La Canada Street
Suite 231 Las Vegas, NV 89169
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Northwest


7445 Peak Drive
Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

Summerlin Hospital Medical Center


657 Town Center Drive
Las Vegas, NV 89144
Map

702-384-0013
research@sncrf.org

Radiation Oncology Centers of Nevada Central


624 South Tonopah Drive
Las Vegas, NV 89106
Map

702-384-0013
research@sncrf.org

Radiation Oncology Associates


6630 B South McCarran
Suite 18 Reno, NV 89509
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Town Center


653 North Town Center Drive
Suite 402 Las Vegas, NV 89144
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada


9280 West Sunset Road
Suite 100 Las Vegas, NV 89148
Map

702-384-0013
research@sncrf.org

Alliance for Childhood Diseases/Cure 4 the Kids Foundation


One Breakthrough Way
Las Vegas, NV 89135
Map

702-384-0013
research@sncrf.org

Hope Cancer Care of Nevada


6827 West Tropicana Avenue
Suite 110 Las Vegas, NV 89103
Map

702-384-0013
research@sncrf.org

Cancer and Blood Specialists-Henderson


2460 West Horizon Ridge Parkway
Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway


3006 South Maryland Parkway
Suite 205 Las Vegas, NV 89109
Map

702-384-0013
research@sncrf.org

University Medical Center of Southern Nevada


1800 West Charleston Boulevard
Las Vegas, NV 89102
Map

702-384-0013
research@sncrf.org

Saint Mary's Regional Medical Center


235 West Sixth Street
Reno, NV 89503
Map

702-384-0013
research@sncrf.org

Renown Regional Medical Center


1155 Mill Street
Reno, NV 89502
Map

702-384-0013
research@sncrf.org

Sunrise Hospital and Medical Center


3186 South Maryland Parkway
Las Vegas, NV 89109
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at Seven Hills


3175 Saint Rose Parkway
Suite 200 Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

Ann M Wierman MD LTD


3150 Tenaya Way
Suite 200 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

Hope Cancer Care of Nevada-Pahrump


2340 East Calvada Boulevard
Suite 7 Pahrump, NV 89048
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada-Horizon Ridge


2460 West Horizon Ridge Parkway
Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

Desert West Surgery


1111 Shadow Lane
Las Vegas, NV 89102
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at MountainView


3150 North Tenaya Way
Suite 510 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at Charleston


2300 West Charleston Boulevard
Las Vegas, NV 89102
Map

702-384-0013

Kingman Regional Medical Center


3269 Stockton Hill Road
Kingman, AZ 86401
Map

702-384-0013
research@sncrf.org

Urology Specialists of Nevada - Southwest


8410 West Warm Springs Road
Suite 10 Las Vegas, NV 89113
Map


research@sncrf.org

Urology Specialists of Nevada - Central


2010 Wellness Way
Suite 200 Las Vegas, NV 89106
Map


research@sncrf.org

Las Vegas Urology - Sunset


7150 West Sunset Road
Suite 201A and 202B Las Vegas, NV 89113
Map


research@sncrf.org

Las Vegas Urology - Green Valley


1701 North Green Valley Parkway
Suite 10C Henderson, NV 89074
Map


research@sncrf.org

Urology Specialists of Nevada - Green Valley


58 North Pecos Road
Henderson, NV 89074
Map


research@sncrf.org

Las Vegas Urology - Pecos


9053 South Pecos Road
Suite 2900 Las Vegas, NV 89074
Map


research@sncrf.org

Las Vegas Urology - Pebble


8915 South Pecos Road
Suite 19A Henderson, NV 89074
Map


research@sncrf.org

Las Vegas Urology - Cathedral Rock


7200 Cathedral Rock Drive
Suites 180 and 210 Las Vegas, NV 89128
Map


research@sncrf.org

Las Vegas Prostate Cancer Center


7150 West Sunset Road
Suite 100 Las Vegas, NV 89113
Map


research@sncrf.org

Urology Specialists of Nevada - Northwest


3150 North Tenaya Way
Suite 165 Las Vegas, NV 89128
Map


research@sncrf.org

Valley Medical Center


400 South 43rd Street
Renton, WA 98055
Map

425-228-3440
research@valleymed.org