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Stage IIB Non-Small Cell Lung CancerPhase 2NCT03916419

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

A Phase 2 study testing ViewRay MR-Linear Accelerator, Radiation therapy and Paclitaxel in people with Stage IIB Non-Small Cell Lung Cancer and Stage IIIA Non-small Cell Lung Cancer, run by Washington University School of Medicine at 1 site in United States.

Completed

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

Official record

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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ViewRay MR-Linear Accelerator, Radiation therapy and Paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteUnited States
Study dates
20 Jun 2019to 28 Sep 2025
Phase
Phase 2

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

  • 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.
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  • 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
  • Platelets ≥ 100,000 cells/mm3
  • Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.)
  • AST and ALT ≤ 1.5 upper limit of normal within 30 days prior to registration.
  • Total bilirubin ≤ 1.5 upper limit of normal within 30 days prior to registration.
  • Serum creatinine < 1.5 mg/dL or calculated creatinine clearance ≥ 50 mL/min within 30 days prior to registration estimated by the Cockcroft-Gault formula:
  • Creatinine Clearance (male) = [(140 - age) x (wt in kg)] [(Serum Creatinine mg/dl) x (72)] Creatinine Clearance (female) = 0.85 x Creatinine Clearance (male)
  • Peripheral neuropathy ≤ grade 1 at the time of registration.
  • Presence of measurable or evaluable disease by RECIST 1.1.
  • Negative serum or urine pregnancy test within 2 weeks prior to registration for women of childbearing potential.
  • Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study.
  • Able to understand and willing to sign an IRB-approved informed consent document. Patients without capacity to make an informed consent decision must have a legally authorized representative sign the IRB-approved informed consent document on their behalf.

Who cannot join

  • 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
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  • 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
  • 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 CT scan.
  • Chronic oral steroid use (greater than prednisone 10 mg orally once daily, or its equivalent) for any indication.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Single-Arm Phase II Study With a Safety Lead-in of 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

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.

Being tested
ViewRay MR-Linear Accelerator, Radiation therapy, Paclitaxel, Carboplatin AUC, Durvalumab
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • ViewRay MR-Linear AcceleratorDevice

    -Radiation will be delivered by this machine

  • Radiation therapyRadiation

    -60Gy in 15 fractions

  • PaclitaxelDrug

    Also called Taxol

    -50 mg/m^2 intravenous

  • Carboplatin AUCDrug

    Also called Paraplatin

    -2 mg/mL/min intravenous over 30 minutes

  • DurvalumabBiological

    Also called Imfinzi

    -10 mg/kg

Study groups in NCT03916419
Study groupRoleWhat they receive
Safety lead-in: Chemoradiation + DurvalumabExperimental* 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 be administered every 2 weeks or 4 weeks (timeline at the discretion of treating physician) for up to 12 months.
Receives: Device: ViewRay MR-Linear Accelerator; Radiation: Radiation therapy; Drug: Paclitaxel; Drug: Carboplatin AUC; Biological: Durvalumab
Phase II: Chemoradiation + DurvalumabExperimental-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 be administered every 2 weeks or 4 weeks (timeline at the discretion of the treating physician) for up to 12 months.
Receives: Device: ViewRay MR-Linear Accelerator; Radiation: Radiation therapy; Drug: Paclitaxel; Drug: Carboplatin AUC; Biological: Durvalumab

What is being measured

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

  1. 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.

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

  2. Local Control Rate

    -Defined as percentage of participants who do not have clinical and/or radiographic evidence of progression of disease at the primary (local) site

    Measured: Through completion of follow-up (median 731 days, full range: 72 days-1162 days)

  3. Regional Control Rate

    -Defined as the percentage of participants who do not have clinical and/or radiographic evidence of progression of disease at the previously involved or uninvolved hilar and/or mediastinal nodal (regional) sites

    Measured: Through completion of follow-up (median time 731 days, full range: 72 - 1162 days)

Secondary outcomes (8)

  1. Number of Participants With Acute Toxicities by Worst Grade Experienced

    -Graded per NCI CTCAE version 5.0

    Measured: From start of chemoradiation through 60 days

  2. Number of Participants With Late Toxicities by Worst Grade Experienced

    Graded per NCI CTCAE version 5.

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

  3. Tumor Response Rate

    -Tumor response is defined as achieving a partial or complete response per RECIST criteria.

    Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level.

    Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

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

  4. Distant Control Rate

    -Defined as the number of participants who did not have distant recurrence. Distant recurrence is defined as the development of metastatic, non-local, and non-regional disease.

    Measured: Through completion of follow-up (median 731 days, full range: 72 days - 1162 days)

  5. Incidence of Brain Metastases

    -Defined as the percentage of participants who develop brain metastases.

    Measured: Through completion of follow-up (median 731 days, full range: 72 days - 1162 days)

  6. Median Progression-free Survival (PFS) Probability

    • PFS is defined as the months from start date of chemoradiation to either date of progression or death, whichever occurs first. Alive patients without progression are censored at the date of last follow-up or visit.
    • Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

    Measured: Through completion of follow-up (median 731 days, full range: 72 days - 1162 days)

  7. Median Disease-free Survival (DFS) Probability

    DFS is defined as survival with no evidence of recurrent (local, regional or distant) disease or death

    Measured: Through completion of follow-up (median 731 days, full range: 72 days - 1162 days)

  8. Median Overall Survival (OS) Probability

    OS is defined as the months from the start date of chemoradiation to the date of death. Alive patients are censored at the date of last follow-up or visit.

    Measured: Through completion of follow-up (median 731 days, full range: 72 days - 1162 days)

Timeline

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

  1. First posted16 Apr 2019
  2. Study start20 Jun 2019
  3. Primary completion28 Sep 2025
  4. Study completion28 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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03916419
Sponsor's protocol ID
201905035
Status last verified
Sep 2026
First submitted
12 Apr 2019
Last updated
6 Oct 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
No

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