Magnetic Resonance-Guided Hypofractionated Adaptive Radiation Therapy With Concurrent Chemotherapy and Consolidation Durvalumab for Inoperable Stage IIB, IIIA, and Select IIIB and IIIC Non-small Cell Lung Cancer

NCT03916419 | Completed Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: 201905035
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Building upon the clinical experience of the investigators with the magnetic resonance (MR)-guided radiation therapy system and applying principals of hypofractionation toward the current treatment paradigm of concurrent chemoradiation and consolidation immunotherapy for locally advanced non-small cell lung cancer (NSCLC), this prospective, single-arm Phase II clinical trial with safety lead-in will test the feasibility and outcomes of this approach.

Conditions

Stage IIB Non-Small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIC Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

• Safety lead-in only: Number of participants with dose limiting toxicities (DLTs)

  * Safety of hypofractionated MRI-guided adaptive radiotherapy (60Gy/15 fractions) with concurrent chemotherapy (carboplatin and paclitaxel) and consolidation durvalumab is defined as \<2/6 participants experiencing dose limiting toxicities * DLT is defined as any possibly, probably, or definitely related to concurrent chemoradiation grade 3 toxicity that cannot be managed with maximal supportive care within 2 weeks, or any grade \> 4 toxicity that occurs during treatment * The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.

  Through 6 months after completion of concurrent chemoradiation (estimated to be 6 months and 3 weeks)

• Local control rate (Phase II only)

  -Clinical and/or radiographic evidence of progression of disease at the primary (local) site

  Through 2 years after start of chemoradiation (estimated to be 2 years and 3 weeks)

• Regional control rate (Phase II only)

  -Clinical and/or radiographic evidence of progression of disease at the previously involved or uninvolved hilar and/or mediastinal nodal (regional) sites

  Through 2 years after start of chemoradiation (estimated to be 2 years and 3 weeks)

Secondary Outcomes (8)

• Number of acute toxicities

  From start of chemoradiation through 60 days

• Number of late toxicities

  From 61 days after start of chemoradiation through 2 years after the start of chemoradiation

• Tumor response rate

  Through completion of treatment (estimated to be 12 months and 3 weeks)

• Distant recurrence rate

  Through 2 years after start of chemoradiation (estimated to be 2 years and 3 weeks)

• Incidence of brain metastases

  Through 2 years after start of chemoradiation (estimated to be 2 years and 3 weeks)

Study Arms (2)

Safety lead-in: Chemoradiation + Durvalumab

EXPERIMENTAL

* The first 6 patients enrolled on study will comprise the Safety Lead-In cohort and will be closely monitored for toxicity related specifically to the experimental chemoradiation portion of the study treatment. After these 6 patients have been enrolled, accrual will temporarily be suspended for a minimum of 6 months after completion of chemoradiation to allow for the evaluation of adverse events. * Patients will receive concurrent chemoradiation over the course of 3 weeks (15 fractions of radiation with online adaptive treatment planning at fractions 6, 9, and 12 and weekly carboplatin + paclitaxel). Four to 6 weeks after the end of chemoradiation, durvalumab immunotherapy will administered every 2 weeks or 4 weeks (timeline at the discretion of treating physician) for up to 12 months.

Device: ViewRay MR-Linear Accelerator; Radiation: Radiation therapy; Drug: Paclitaxel; Drug: Carboplatin AUC; Biological: Durvalumab

Phase II: Chemoradiation + Durvalumab

EXPERIMENTAL

-Patients will receive concurrent chemoradiation over the course of 3 weeks (15 fractions of radiation with online adaptive treatment planning at fractions 6, 9, and 12 and weekly carboplatin + paclitaxel). Four to 6 weeks after the end of chemoradiation, durvalumab immunotherapy will administered every 2 weeks or 4 weeks (timeline at the discretion of the treating physician) for up to 12 months.

Device: ViewRay MR-Linear Accelerator; Radiation: Radiation therapy; Drug: Paclitaxel; Drug: Carboplatin AUC; Biological: Durvalumab

Interventions

ViewRay MR-Linear Accelerator DEVICE

-Radiation will be delivered by this machine

Phase II: Chemoradiation + Durvalumab; Safety lead-in: Chemoradiation + Durvalumab

Radiation therapy RADIATION

-60Gy in 15 fractions

Phase II: Chemoradiation + Durvalumab; Safety lead-in: Chemoradiation + Durvalumab

Paclitaxel DRUG

-50 mg/m\^2 intravenous

Also known as: Taxol

Phase II: Chemoradiation + Durvalumab; Safety lead-in: Chemoradiation + Durvalumab

Carboplatin AUC DRUG

-2 mg/mL/min intravenous over 30 minutes

Also known as: Paraplatin

Phase II: Chemoradiation + Durvalumab; Safety lead-in: Chemoradiation + Durvalumab

Durvalumab BIOLOGICAL

-10 mg/kg

Also known as: Imfinzi

Phase II: Chemoradiation + Durvalumab; Safety lead-in: Chemoradiation + Durvalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically proven diagnosis of non-small cell lung cancer.
• Inoperable or patient has refused surgery
• Clinical AJCC stage IIB or IIIA (AJCC, 8th ed.) with plans to be treated with concurrent chemoradiotherapy.
• Recurrent non-small cell lung cancer is allowed, provided the intent of the current treatment is curative and there has been no prior radiation to the thorax (except prior SBRT per the protocol)
• Prior chemotherapy, immunotherapy, or targeted therapy is permitted as long as patients have recovered from prior toxicities to grade ≤ 1
• Clinical AJCC stage IIIB with plans to be treated with concurrent chemoradiotherapy are eligible if any of the following apply: (1) T3N2M0, (2) T4N2M0 (with T4 by size criteria (\> 7 cm); T4 due to invasion or nodules in other ipsilateral lobe are excluded), (3) T1-2N3M0 where N3 disease is confined to no more than 2 contiguous nodal stations in the contralateral mediastinum. N3 disease with either contralateral hilar adenopathy, multistation contralateral mediastinal adenopathy that is either non-contiguous or \>2 contiguous nodal stations, or any scalene or supraclavicular adenopathy are not eligible.
• Clinical AJCC stage IIIC (T3-4N3M0) are eligible if N3 disease is confined to no more than 2 contiguous nodal stations in the contralateral mediastinum as above and, if applicable, T4 is due only to size \>7 cm as above.
• Appropriate stage for protocol entry based upon the following minimum diagnostic workup:
• History/physical examination within 30 days prior to registration
• FDG-PET/CT scan and CT chest with or without contrast for staging within 60 days prior to registration
• MRI scan with contrast of the brain (preferred) or CT scan of the brain with contrast within 60 days prior to registration
• Zubrod Performance Status 0-2 within 30 days prior to registration.
• Age ≥ 18 years.
• CBC/differential obtained within 30 days prior to registration, with adequate bone marrow function defined as follows:
• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3

You may not qualify if:

• Severe, active comorbidity, defined as follows:
• Unstable angina, history of myocardial infarction and/or congestive heart failure requiring hospitalization within the last 6 months
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
• Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol
• Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients
• Prior radiotherapy to the thorax. An exception can be made for prior stereotactic body radiation therapy (SBRT) if there is no overlap with the protocol PTV and OAR constraints can still be achieved with a composite plan.
• Evidence of a concurrent primary malignancy, or any history of metastatic cancer.
• Currently receiving any other investigational agents.
• Pregnant or breastfeeding.
• Medical contraindication to receiving MRI imaging (including presence of a cardiac pacemaker).
• Autoimmune disease requiring active treatment, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis. Specific instances of autoimmune disease are eligible and allowed on study, as below:
• Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone
• Patients with controlled type 1 diabetes mellitus on a stable insulin regimen.
• Patients with eczema or psoriasis with dermatologic manifestations only, provided that the disease is well controlled at baseline and only requiring topical steroids, with no acute exacerbations within the last 12 months (requiring psoralen, ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high potency or oral steroids

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Radiotherapy; Paclitaxel; Carboplatin; durvalumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• Gregory Vlacich, M.D, Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2019
• First Posted: April 16, 2019
• Study Start: June 20, 2019
• Primary Completion: September 28, 2025
• Study Completion: September 28, 2025
• Last Updated: November 12, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)