Clinical Trials Directory

Trials / Completed

CompletedNCT03801902

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

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)

Status
Completed
Phase
Phase 1
Study type
Interventional
Enrollment
26 (actual)
Sponsor
National Cancer Institute (NCI) · NIH
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

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 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.

Detailed description

PRIMARY OBJECTIVES: I. 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: I. 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: I. 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.

Conditions

Interventions

TypeNameDescription
RADIATIONAccelerated Hypofractionated Radiation Therapy160 Gy given as one 4 Gy fraction per day, 5 days per week for 15 fractions.
PROCEDUREBiospecimen CollectionUndergo collection of blood samples
PROCEDUREComputed TomographyUndergo brain CT and chest CT
BIOLOGICALDurvalumabAdministered 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.
PROCEDUREMagnetic Resonance Imaging of the Brain with and without ContrastUndergo brain MRI
BIOLOGICALMonalizumabAdministered IV as a 1500 mg fixed dose over 60 minutes (+/- 10 minutes)
BIOLOGICALOleclumabAdministered IV 3000 mg over 60 minutes (+/- 10 minutes)
RADIATIONRadiation Therapy60 gy given as one 2 Gy fraction per day, 5 days per week for 30 fractions

Timeline

Start date
2019-10-28
Primary completion
2021-10-26
Completion
2025-09-04
First posted
2019-01-14
Last updated
2025-09-23
Results posted
2025-06-19

Locations

56 sites across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT03801902. Inclusion in this directory is not an endorsement.