AzTrials
AzTrials

Locally Advanced Lung Non-Small Cell CarcinomaPhase 1NCT03801902

Testing the Safety of Adding Either Monalizumab (IPH2201) or Oleclumab (MEDI9447) to Durvalumab (MEDI4736) Plus Standard Radiation Therapy for Locally Advanced Non-small Cell Lung Cancer (NSCLC), ARCHON-1 Trial

A Phase 1 study testing Accelerated Hypofractionated Radiation Therapy, Biospecimen Collection and Computed Tomography in people with Locally Advanced Lung Non-Small Cell Carcinoma and Locally Recurrent Lung Non-Small Cell Carcinoma, run by National Cancer Institute (NCI) at 56 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase I trial studies the safety of adding durvalumab to accelerated hypofractionated radiation therapy (ACRT) or conventionally fractionated radiation therapy, as well as the safety of adding either monalizumab or oleclumab to durvalumab plus conventionally fractionated radiation therapy in treating patients… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Accelerated Hypofractionated Radiation Therapy, Biospecimen Collection and Computed Tomography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
56 sitesUnited States
Study dates
28 Oct 2019to 4 Sep 2025
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Pathologic (cytological or histological) proof of diagnosis of stage II-III (American Joint Committee on Cancer [AJCC] 8th edition [ed.]) unresectable or inoperable, non-metastatic non-small cell lung cancer (NSCLC) within 60 days prior to registration, with no liver or renal end organ damage, as determined by normal laboratory values noted below. Locally recurrent, N1-N3 disease following surgery without prior radiation therapy is eligible. Patients with N1 to N3 and undetectable primary lung tumors (T0) are eligible
  • Pathological diagnosis of PD-L1 high expressing tumors (>= 50%) within 60 days prior to registration (using Dako 22C3 immunohistochemistry [IHC] antibody or the Ventana SP263 antibody platforms) performed at a Clinical Laboratory Improvement Act (CLIA)-certified lab
  • Appropriate stage for study entry based on the following diagnostic workup:
  • History/physical examination within 30 days prior to registration;
  • Positron emission tomography (PET)/computed tomography (CT) scan for staging within 30 days prior to registration (note: if CT portion of PET/CT scan is not of diagnostic quality, then a separate CT scan with contrast is required);
  • Magnetic resonance imaging (MRI) scan of the brain with contrast; if medically contraindicated, then CT scan of the brain with contrast (unless medically contraindicated) is acceptable, within 30 days prior to registration;
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  • Sufficient lung function with forced expiratory volume in 1 second (FEV1) >= 0.8 liter or >= 35% predicted and carbon monoxide diffusing capability (DLCO) >= 40% with or without bronchodilator within 30 days prior to registration;
  • Patients who meet the criterion above without oxygen (O2), but who need acute (started within 10 days prior to registration) supplemental oxygen due to tumor-caused obstruction/hypoxia are eligible, provided the amount of the O2 needed has been stable
  • Age ≥ 18
  • Minimum body weight >= 40 kg
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 30 days prior to registration
  • Absolute neutrophil count (ANC) >= 1500 cells/mm^3 (within 30 days prior to registration)
  • Lymphocyte count >= 500 cells/mm^3 (within 30 days prior to registration)
  • Platelet count >= 100,000 cells/mm^3 (within 30 days prior to registration)
  • Hemoglobin >= 9.0 g/dL (within 30 days prior to registration) (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 9.0 g/dl is acceptable)
  • Creatinine clearance >= 40 mL/min by the Cockcroft-Gault (C-G) equation
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) with the following exception (within 30 days prior to registration):
  • Patients with known Gilbert disease who have serum bilirubin level =< 3 x ULN may be enrolled
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN (within 30 days prior to registration)
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients, obtained within 14 days prior to registration. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
  • Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
  • Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
  • Patients who are human immunodeficiency virus (HIV) positive may participate IF they meet 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
  • They must not be receiving prophylactic therapy for an opportunistic infection
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

Who cannot join

  • Definitive clinical or radiologic evidence of metastatic disease
  • Prior invasive malignancy (except those with a negligible risk of metastasis or death and with expected curative outcome [such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent] or undergoing active surveillance per standard-of-care management [e.g., chronic lymphocytic leukemia (CLL) Rai stage 0, prostate cancer with Gleason score =< 6, and prostate specific antigen (PSA) =< 10 mg/mL]) unless disease free for a minimum of 3 years
  • Prior chemotherapy or systemic therapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields so that cumulative composite dose combining previous plan and current plan to be within 80 Gy to the trachea, major blood vessels, esophagus, and heart, and 55 Gy to the spinal cord (if such patients are being considered, this will need to be centrally reviewed). Prior chest radiation without overlap is permissible
  • Prior history of myocardial infarction, stroke, or transient ischemic attack in the past 3 months
  • History of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Patients with a history of treated autoimmune thyroid disease requiring thyroid replacement but not immunosuppressives, as well as type 1 diabetes, are permitted. Patients with vitiligo, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
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  • 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 chest PET/CT or CT scan
  • Severe, active co-morbidity defined as follows:
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease;
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications;
  • Active tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice);
  • 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, a positive anti-HBc (antibody to hepatitis B core antigen), and a negative viral deoxyribonucleic acid (DNA) test (only obtained if HBsAg is found positive) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception during treatment and for 3 months after the last dose of treatment; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
  • Women who are breastfeeding and unwilling to discontinue
  • Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade >= 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria:
  • Patients with grade >= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician.
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the study physician
  • Major surgical procedure (as defined by the investigator) within 28 days prior to registration
  • Note:
  • Local surgery of isolated lesions for palliative intent is acceptable
  • Other major surgery before first dose of immunotherapy is not acceptable
  • History of allogenic organ transplantation
  • History of leptomeningeal carcinomatosis
  • History of active primary immunodeficiency
  • Current or prior use of immunosuppressive medication within 14 days before registration. (Note: immunosuppressive medication within 14 days before immunotherapy is not acceptable). The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection);
  • Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of prednisone or its equivalent;
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  • Receipt of live attenuated vaccine within 30 days prior to registration
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients

Trial locations and contacts

56 sites in 1 country.

56 sites in 1 country

United States56 sites

  • Grady Health System

    Atlanta, Georgia, 30303

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Emory Saint Joseph's Hospital

    Atlanta, Georgia, 30342

  • Augusta University Medical Center

    Augusta, Georgia, 30912

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • McLaren Cancer Institute-Bay City

    Bay City, Michigan, 48706

  • UM Upper Chesapeake Medical Center

    Bel Air, Maryland, 21014

  • Saint Alphonsus Cancer Care Center-Boise

    Boise, Idaho, 83706

  • Saint Alphonsus Cancer Care Center-Caldwell

    Caldwell, Idaho, 83605

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • McLaren Cancer Institute-Clarkston

    Clarkston, Michigan, 48346

  • Michigan Healthcare Professionals Clarkston

    Clarkston, Michigan, 48346

  • Central Maryland Radiation Oncology in Howard County

    Columbia, Maryland, 21044

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • MD Anderson in The Woodlands

    Conroe, Texas, 77384

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Saint Elizabeth Healthcare Edgewood

    Edgewood, Kentucky, 41017

  • Michigan Healthcare Professionals Farmington

    Farmington Hills, Michigan, 48334

  • Weisberg Cancer Treatment Center

    Farmington Hills, Michigan, 48334

  • McLaren Cancer Institute-Flint

    Flint, Michigan, 48532

  • Singh and Arora Hematology Oncology PC

    Flint, Michigan, 48532

  • UM Baltimore Washington Medical Center/Tate Cancer Center

    Glen Burnie, Maryland, 21061

  • Benefis Sletten Cancer Institute

    Great Falls, Montana, 59405

  • Legacy Mount Hood Medical Center

    Gresham, Oregon, 97030

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • MD Anderson West Houston

    Houston, Texas, 77079

  • Logan Health Medical Center

    Kalispell, Montana, 59901

  • University of Kansas Cancer Center-West

    Kansas City, Kansas, 66112

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • University of Kansas Cancer Center - North

    Kansas City, Missouri, 64154

  • Karmanos Cancer Institute at McLaren Greater Lansing

    Lansing, Michigan, 48910

  • Mid-Michigan Physicians-Lansing

    Lansing, Michigan, 48912

  • McLaren Cancer Institute-Lapeer Region

    Lapeer, Michigan, 48446

  • MD Anderson League City

    League City, Texas, 77573

  • University of Kansas Cancer Center - Lee's Summit

    Lee's Summit, Missouri, 64064

  • West Virginia University Healthcare

    Morgantown, West Virginia, 26506

  • McLaren Cancer Institute-Macomb

    Mount Clemens, Michigan, 48043

  • Saint Alphonsus Cancer Care Center-Nampa

    Nampa, Idaho, 83687

  • University of Kansas Cancer Center at North Kansas City Hospital

    North Kansas City, Missouri, 64116

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Nebraska Methodist Hospital

    Omaha, Nebraska, 68114

  • University of Kansas Cancer Center-Overland Park

    Overland Park, Kansas, 66210

  • McLaren Cancer Institute-Northern Michigan

    Petoskey, Michigan, 49770

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • McLaren-Port Huron

    Port Huron, Michigan, 48060

  • Legacy Good Samaritan Hospital and Medical Center

    Portland, Oregon, 97210

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

  • MD Anderson in Sugar Land

    Sugar Land, Texas, 77478

  • Michigan Healthcare Professionals Troy

    Troy, Michigan, 48098

  • Legacy Salmon Creek Hospital

    Vancouver, Washington, 98686

  • University of Kansas Hospital-Westwood Cancer Center

    Westwood, Kansas, 66205

  • Lankenau Medical Center

    Wynnewood, Pennsylvania, 19096

Other trials in United States

About this study

Official title: Phase I Trial of Radiotherapy Combined With Durvalumab Alone Plus Either Monalizumab or Oleclumab in PD-L1 High Locally Advanced Non-Small Cell Lung Cancer (NSCLC) (ARCHON-1)

This phase I trial studies the safety of adding durvalumab to accelerated hypofractionated radiation therapy (ACRT) or conventionally fractionated radiation therapy, as well as the safety of adding either monalizumab or oleclumab to durvalumab plus conventionally fractionated radiation therapy in treating patients with non-small cell lung cancer that has spread to nearby tissue or lymph nodes (locally advanced). Accelerated hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Immunotherapy with monoclonal antibodies, such as durvalumab and monalizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Oleclumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD73, which is found on some types of tumor cells. Oleclumab may block CD73 and help the immune system kill tumor cells. It is not yet known whether adding durvalumab to ACRT or adding monalizumab or oleclumab to durvalumab plus conventionally fractionated radiation therapy will work better in treating patients with non-small cell lung cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate if the addition of durvalumab to two schedules of radiation therapies (60 Gy in 30 fractions or 60 Gy in 15 fractions) is safe.

II. To evaluate if the addition of either monalizumab or oleclumab to radiation therapy (RT) (60 Gy in 30 fractions) + durvalumab is safe.

SECONDARY OBJECTIVES:

  1. To examine if the addition of durvalumab to radiation therapy as well as the addition of either monalizumab or oleclumab is feasible.

II. To assess toxicities associated with the addition of durvalumab to radiation therapy as well as the addition of either monalizumab or oleclumab.

III. To obtain preliminary estimates of progression-free survival (PFS), using Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, in patients who received durvalumab added to radiation, and either monalizumab or oleclumab added to RT (60 Gy in 30 fractions) + durvalumab.

EXPLORATORY OBJECTIVES:

  1. To assess the impact the addition of durvalumab to RT and either monalizumab or oleclumab to RT (60 Gy in 30 fractions) + durvalumab have on progression-free survival, using Immune-Related Response Criteria (irRC) guidelines.

II. To assess the changes in circulating tumor cells (CTCs) and various immune parameters during treatment with durvalumab and radiotherapy and changes after completion of treatment.

OUTLINE: Patients are randomized to Arm I or Arm II (CLOSED TO ACCRUAL).

ARM I (CLOSED): Starting 2 weeks prior to radiation therapy, patients receive durvalumab intravenously (IV) over 60 minutes on day 1 of each cycle. Treatment repeats every 4 weeks for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo accelerated hypofractionated radiation therapy (ACRT) 1 fraction per day, 5 days per week for 15 fractions. Patients also undergo brain magnetic resonance imaging (MRI) or computed tomography (CT) scan during screening and as clinically indicated, chest CT scans on study and during follow up, and collection of blood samples during screening and on study.

ARM II (CLOSED): Starting 2 weeks prior to radiation therapy, patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Treatment repeats every 4 weeks for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo conventionally fractionated radiation therapy 1 fraction per day, 5 days per week for 30 fractions. Patients also undergo brain MRI or CT scan during screening and as clinically indicated, chest CT scans on study and during follow up, and collection of blood samples during screening and on study.

Patients are assigned to Arm III or Arm IV.

ARM III: Starting 2 weeks prior to radiation therapy, patients receive durvalumab IV over 60 minutes and monalizumab IV over 60 minutes on day 1 of each cycle. Treatment repeats every 4 weeks for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo conventionally fractionated radiation therapy 1 fraction per day, 5 days per week for 30 fractions. Patients also undergo brain MRI or CT scan during screening and as clinically indicated, chest CT scans on study and during follow up, and collection of blood samples during screening and on study.

ARM IV: Starting 2 weeks prior to radiation therapy, patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Patients also receive oleclumab IV over 60 minutes on days 1 and 15 of cycles 1-2, then on day 1 of cycles thereafter. Treatment repeats every 4 weeks for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo conventionally fractionated radiation therapy 1 fraction per day, 5 days per week for 30 fractions. Patients also undergo brain MRI or CT scan during screening and as clinically indicated, chest CT scans on study and during follow up, and collection of blood samples during screening and on study.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 4 months for 1 year.

Being tested
Accelerated Hypofractionated Radiation Therapy, Biospecimen Collection, Computed Tomography, Durvalumab, Magnetic Resonance Imaging of the Brain with and without Contrast
Medical subject headings
Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Accelerated Hypofractionated Radiation TherapyRadiation

    Also called AHF-RT, AHRT

    160 Gy given as one 4 Gy fraction per day, 5 days per week for 15 fractions.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo collection of blood samples

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo brain CT and chest CT

  • DurvalumabBiological

    Also called Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI 4736, MEDI-4736

    Administered intravenously (IV) as a 1500 mg fixed dose over 60 minutes for 13 cycles (1 cycle = 4 weeks), until disease progression or toxicity or death, whichever comes first.

  • Magnetic Resonance Imaging of the Brain with and without ContrastProcedure or surgery

    Also called Brain Magnetic Resonance Imaging with and without Contrast, Brain MRI, Brain MRI with and without Contrast, Head MRI with and without Contrast

    Undergo brain MRI

  • MonalizumabBiological

    Also called Immunoglobulin G4-kappa, Anti-(Homo sapiens KLRC1 (Killer Cell Lectin-like Receptor Subfamily C Member 1, NKG2-a, NKG2a, CD159A, CD94)), Humanized Monoclonal Antibody, IPH-2201, IPH2201, NN-8765

    Administered IV as a 1500 mg fixed dose over 60 minutes (+/- 10 minutes)

  • OleclumabBiological

    Also called Anti-CD73 Monoclonal Antibody MEDI9447, MEDI9447

    Administered IV 3000 mg over 60 minutes (+/- 10 minutes)

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate

    60 gy given as one 2 Gy fraction per day, 5 days per week for 30 fractions

Study groups in NCT03801902
Study groupRoleWhat they receive
Arm I (CLOSED) (Durvalumab and ACRT)ExperimentalStarting 2 weeks prior to radiation therapy, patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Treatment repeats every 4 weeks for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo ACRT 1 fraction per day, 5 days per week for 15 fractions. Patients also undergo brain MRI or CT scan during screening and as clinically indicated, chest CT scans on study and during follow up, and collection of blood samples during screening and on study.
Receives: Radiation: Accelerated Hypofractionated Radiation Therapy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Durvalumab; Procedure: Magnetic Resonance Imaging of the Brain with and without Contrast
Arm II (CLOSED) (Durvalumab and standard RT)ExperimentalStarting 2 weeks prior to radiation therapy, patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Treatment repeats every 4 weeks for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo conventionally fractionated radiation therapy 1 fraction per day, 5 days per week for 30 fractions. Patients also undergo brain MRI or CT scan during screening and as clinically indicated, chest CT scans on study and during follow up, and collection of blood samples during screening and on study.
Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Durvalumab; Procedure: Magnetic Resonance Imaging of the Brain with and without Contrast; Radiation: Radiation Therapy
Arm III (durvalumab, monalizumab, standard RT)ExperimentalStarting 2 weeks prior to radiation therapy, patients receive durvalumab IV over 60 minutes and monalizumab IV over 60 minutes on day 1 of each cycle. Treatment repeats every 4 weeks for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo conventionally fractionated radiation therapy 1 fraction per day, 5 days per week for 30 fractions. Patients also undergo brain MRI or CT scan during screening and as clinically indicated, chest CT scans on study and during follow up, and collection of blood samples during screening and on study.
Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Durvalumab; Procedure: Magnetic Resonance Imaging of the Brain with and without Contrast; Biological: Monalizumab; Radiation: Radiation Therapy
Arm IV (durvalumab, oleclumab, standard RT)ExperimentalStarting 2 weeks prior to radiation therapy, patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Patients also receive oleclumab IV over 60 minutes on days 1 and 15 of cycles 1-2, then on day 1 of cycles thereafter. Treatment repeats every 4 weeks for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo conventionally fractionated radiation therapy 1 fraction per day, 5 days per week for 30 fractions. Patients also undergo brain MRI or CT scan during screening and as clinically indicated, chest CT scans on study and during follow up, and collection of blood samples during screening and on study.
Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Durvalumab; Procedure: Magnetic Resonance Imaging of the Brain with and without Contrast; Biological: Oleclumab; Radiation: Radiation Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Experiencing a Safety Event

    Safety event is defined as one of the following:

    • Grade 4-5 non-hematologic protocol-defined serious adverse event (SAE) possibly, probably, or definitely related to protocol treatment occurring within 90 days from radiation therapy (RT) start for Arm 1 or within 8 weeks from RT start for Arm 2;
    • Any adverse event possibly, probably, or definitely related to protocol treatment that leads to missing at least 2 doses of durvalumab within 90 days from RT start for Arm 1 or within 8 weeks from RT start for Arm 2;
    • Permanent discontinuation of durvalumab due to an adverse event possibly, probably, or definitely related to protocol treatment within the first 30 days of starting durvalumab; or
    • SAEs possibly, probably, or definitely related to RT that cause either an interruption or early termination of RT.

    Adverse events are graded according to the Common Terminology Criteria for Adverse Events version 5.0, which assigns a grade according to severity from 1=mild to 5=death.

    Measured: From start of study treatment to 90 (ACRT) or 56 (standard RT) days from the end of radiation treatment. (Approximately 104 or 70 days, respectively, from start of study treatment)

Secondary outcomes (5)

  1. Percentage of Participants Who Received at Least 80% of Planned Durvalumab Dose During First 8 Weeks Following Initial Dose

    Measured: From start of durvalumab to 8 weeks

  2. Percentage of Participants Who Received at Least 80% of Planned Dose of Monalizumab or Oleclumab During the First 8 Weeks Following the Initial Dose (Feasibility)

    An observation of at least 80% of patients who received at least 80% of the planned dose is considered to be evidence that the given regimen is feasible in this setting.

    Measured: From start of monalizumab or oleclumab to 8 weeks

  3. Distribution of Participants by Highest Grade Adverse Event

    Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 grades adverse event severity from 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.

    Measured: From registration to last follow-up at time of initial analysis. Maximum follow-up was 23.2 months

  4. Percentage of Participants Experiencing a Grade 4 or Higher Non-hematologic Adverse Event

    Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 grades adverse event severity from 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.

    Measured: From registration to last follow-up at time of initial analysis. Maximum follow-up was 23.2 months.

  5. Progression-free Survival

    Progression is defined by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as an increase >= 20% of the sum of longest diameters of target lesions compared with nadir (minimum 5 mm) or progression of non-target lesions or new lesion. Progression-free survival time is defined as time from registration to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. Analysis was planned to occur two years after end of protocol treatment, which could last up to 12 months. No formal testing was planned due to a lack of statistical power.

    Measured: From registration to two years after protocol treatment, which lasted up to 12 months. Maximum follow-up was 38.3 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jan 2019
  2. Study start28 Oct 2019
  3. Primary completion26 Oct 2021
  4. Study completion4 Sep 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03801902
Sponsor's protocol ID
NCI-2019-00176
Other IDs
NCI-2019-00176, NRG-LU004, NRG-LU004, U10CA180868
Status last verified
Sep 2025
First submitted
11 Jan 2019
Last updated
23 Sep 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Accelerated Hypofractionated Radiation Therapy, Biospecimen Collection and Computed Tomography in people with Locally Advanced Lung Non-Small Cell Carcinoma and Locally Recurrent Lung Non-Small Cell Carcinoma, run by National Cancer Institute (NCI) at 56 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 56 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Experiencing a Safety Event (time frame: From start of study treatment to 90 (ACRT) or 56 (standard RT) days from the end of radiation treatment. (Approximately 104 or 70 days, respectively, from start of study treatment)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03801902.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2025.

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