Study of Durvalumab Following Radiation Therapy in Patients With Stage 3 Unresectable NSCLC Ineligible for Chemotherapy (DUART)

January 5, 2024 updated by: AstraZeneca

A Phase II, Open-label, Multicenter, International Study of Durvalumab Following Radiation Therapy in Patients With Stage III, Unresectable Non-Small Cell Lung Cancer Who Are Ineligible for Chemotherapy

This is a Phase II open-label, single-arm, multicenter, international study to evaluate the clinical activity of durvalumab in patients with Stage III unresectable NSCLC who are deemed to be ineligible for chemotherapy per Investigator assessment. Patients will be enrolled into 2 cohorts according to radiotherapy pretreatment dose (Cohort A: standard radiation therapy [60 gray (Gy) ± 10% or hypofractionated bioequivalent dose (BED)]; Cohort B: palliative radiation therapy [40 to < 54 Gy or hypofractionated BED])

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

This is a Phase II open-label, single-arm, multicenter, international study to evaluate the clinical activity of durvalumab in patients with Stage III unresectable NSCLC who have an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 2 and who were treated with radiotherapy but are ineligible for chemotherapy. Patients will be enrolled into 2 cohorts according to the dose of radiotherapy received prior to study entry (Cohort A: Standard Radiotherapy [60 Gy ± 10% or hypofractionated BED]; Cohort B: Palliative Radiotherapy [40 to < 54 Gy or hypofractionated BED]). Patients must not have progressed following radiation therapy, and radiation therapy must be completed within 6 weeks (42 days) prior to first study drug administration. The last dose of radiation therapy is defined as the day of the last radiation treatment session. All patients will receive 1500 mg durvalumab via IV infusion every 4 weeks (q4w) for up to a maximum of 12 months (up to 13 doses/cycles)

Study Type

Interventional

Enrollment (Actual)

102

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Limoges, France, 87000
        • Research Site
      • Marseille, France, 13009
        • Research Site
      • Montpellier, France, 34070
        • Research Site
      • Nimes, France, 30029
        • Research Site
      • Rouen, France, 76031
        • Research Site
      • Brescia, Italy, 25100
        • Research Site
      • Firenze, Italy, 50134
        • Research Site
      • Genova, Italy, 16132
        • Research Site
      • Meldola, Italy, 47014
        • Research Site
      • Messina, Italy, 98158
        • Research Site
      • Modena, Italy, 41124
        • Research Site
      • Monza, Italy, 20900
        • Research Site
      • Negrar, Italy, 37024
        • Research Site
      • Pavia, Italy, 27100
        • Research Site
      • Pisa, Italy, 56124
        • Research Site
      • Ravenna, Italy, 48121
        • Research Site
      • Roma, Italy, 00128
        • Research Site
      • Białystok, Poland, 15-044
        • Research Site
      • Gdańsk, Poland, 80-214
        • Research Site
      • Olsztyn, Poland, 10-228
        • Research Site
      • Szczecin, Poland, 71-730
        • Research Site
      • Warszawa, Poland, 02-781
        • Research Site
      • St. Petersburg, Russian Federation, 197758
        • Research Site
      • St. Petersburg, Russian Federation, 197002
        • Research Site
      • Ufa, Russian Federation, 450054
        • Research Site
      • A Coruña, Spain, 15006
        • Research Site
      • Barcelona, Spain, 8035
        • Research Site
      • Castello de la Plana, Spain, 12002
        • Research Site
      • Madrid, Spain, 28050
        • Research Site
      • Oviedo, Spain, 33011
        • Research Site
      • Pamplona, Spain, 31008
        • Research Site
      • Sabadell(Barcelona), Spain, 08208
        • Research Site
    • Arizona
      • Tucson, Arizona, United States, 85704
        • Research Site
    • Florida
      • Tampa, Florida, United States, 33612
        • Research Site
    • Michigan
      • Royal Oak, Michigan, United States, 48073
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 130 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Capable of giving signed informed consent.
  2. Age ≥ 18 years at study entry.
  3. Histologically or cytologically documented NSCLC with locally-advanced, unresectable Stage III disease.
  4. Deemed ineligible for chemotherapy per Investigator assessment.
  5. Receipt of radiation therapy that was completed within 42 days prior to first study drug administration.
  6. Must have received a total dose of radiation of 40 to 66 Gy (standard or hypofractionated BED).
  7. Must not have progressed following radiation therapy, as per Investigator assessed RECIST 1.1 criteria: a) Patients with measurable disease and/or nonmeasurable and/or no evidence of disease assessed at baseline by computed tomography /magnetic resonance imaging will be eligible for this study. b) Prior irradiated lesions may be considered measurable and selected as target lesions (TLs) providing they fulfill the other criteria for measurability.
  8. World Health Organization/ECOG performance status of ≤2.
  9. No prior exposure to immune-mediated therapy including, but not limited to, anti-CTLA-4, anti-PD-1, anti-PD-L1, and antiprogrammed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines.
  10. Patients must have adequate organ and marrow function as defined below:

    • Hemoglobin ≥ 9.0 g/dL
    • Absolute neutrophil count ≥ 1.0 × 109 /L
    • Platelet count ≥ 75 × 109/L
    • Serum bilirubin ≤ 1.5 × the upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome.
    • Alanine aminotransferase and aspartate aminotransferase ≤ 2.5 × ULN
    • Measured creatinine clearance > 30 mL/min or calculated CL > 30 mL/min as determined by Cockcroft-Gault
  11. Life expectancy of greater than 12 weeks.
  12. Body weight greater than 30 kg at study entry and at first study drug administration

Exclusion Criteria:

  1. Patients with locally-advanced NSCLC whose disease has progressed following radiation therapy.
  2. Mixed small cell lung cancer and NSCLC histology.
  3. History of allogeneic organ transplantation.
  4. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome).
  5. Uncontrolled intercurrent illness (e.g., ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris)
  6. History of another primary malignancy except for (a) malignancy treated with curative intent and with no known active disease ≥ 5 years before the first study drug administration, (b) adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease, and c) treated carcinoma in situ without evidence of disease.
  7. History of leptomeningeal carcinomatosis
  8. History of active primary immunodeficiency
  9. Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus
  10. Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, lymphopenia, and the laboratory values defined in the inclusion criteria
  11. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
  12. Receipt of live attenuated vaccine within 30 days prior to the first dose of durvalumab
  13. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of durvalumab.
  14. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
  15. Participation in another clinical study with an IP administered in the last 4 weeks.
  16. Concurrent enrollment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study
  17. Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment
  18. Patients who refuse chemotherapy by their own decision.
  19. Involvement in the planning and/or conduct of the study
  20. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control.
  21. Judgment by the Investigator that the patient should not participate in the study
  22. Genetics research study (optional):

Exclusion criteria for participation in the optional genetics research component of the study include: a) Previous allogeneic bone marrow transplant b)Nonleukocyte-depleted whole blood transfusion within 120 days of genetic sample collection.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort A
Patients received standard radiotherapy [60 gray (Gy) ± 10% or hypofractionated BED] prior to study entry.
All patients will receive 1500 mg durvalumab via IV infusion q4w for up to a maximum of 12 months.
Other Names:
  • MEDI4736
Experimental: Cohort B
Patients received palliative radiotherapy [40 to < 54 Gy or hypofractionated BED] prior to study entry.
All patients will receive 1500 mg durvalumab via IV infusion q4w for up to a maximum of 12 months.
Other Names:
  • MEDI4736

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with Grade 3 and Grade 4 possibly-related adverse events (PRAEs)
Time Frame: From screening (day -28) to 6 months from the initiation of durvalumab treatment
To assess the safety and tolerability profile of durvalumab as defined by Grade 3 and Grade 4 PRAEs
From screening (day -28) to 6 months from the initiation of durvalumab treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Progression-free survival (PFS)
Time Frame: From the first date of treatment until the date of objective disease progression or death (up to maximum 12 months)
To assess the efficacy of durvalumab treatment . PFS is defined as the time from the first date of treatment until the date of objective disease progression or death regardless of whether the patient withdraws from investigational product (IP) or receives another anticancer therapy prior to progression
From the first date of treatment until the date of objective disease progression or death (up to maximum 12 months)
PFS at 6 months (PFS6)
Time Frame: From the first date of treatment until the date of objective disease progression or death (up to maximum 6 months)
To assess the efficacy of durvalumab treatment . PFS is defined as the time from the first date of treatment until the date of objective disease progression or death regardless of whether the patient withdraws from IP or receives another anticancer therapy prior to progression
From the first date of treatment until the date of objective disease progression or death (up to maximum 6 months)
PFS at 12 months (PFS12)
Time Frame: From the first date of treatment until the date of objective disease progression or death (up to maximum 12 months)
To assess the efficacy of durvalumab treatment. PFS is defined as the time from the first date of treatment until the date of objective disease progression or death regardless of whether the patient withdraws from IP or receives another anticancer therapy prior to progression
From the first date of treatment until the date of objective disease progression or death (up to maximum 12 months)
Median overall survival (OS)
Time Frame: From the first date of treatment until death due to any cause (up to maximum 12 months)
To assess the efficacy of durvalumab treatment. OS is defined as the time from the first date of treatment until death due to any cause
From the first date of treatment until death due to any cause (up to maximum 12 months)
OS at 12 months (OS12)
Time Frame: From the first date of treatment until death due to any cause (up to maximum 12 months)
To assess the efficacy of durvalumab treatment. OS is defined as the time from the first date of treatment until death due to any cause
From the first date of treatment until death due to any cause (up to maximum 12 months)
Objective response rate (ORR)
Time Frame: From 8 weeks ±1 week after investigational product (IP) treatment initiation and continue every 8 weeks (q8w) ±1 week through 48 weeks and every 12 weeks (q12w) ±1 week until disease progression (up to maximum of 12 months)
To assess the efficacy of durvalumab treatment in terms of ORR based on Investigator assessments per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
From 8 weeks ±1 week after investigational product (IP) treatment initiation and continue every 8 weeks (q8w) ±1 week through 48 weeks and every 12 weeks (q12w) ±1 week until disease progression (up to maximum of 12 months)
Duration of response (DoR)
Time Frame: From 8 weeks ±1 week after IP treatment initiation and continue q8w ±1 week through 48 weeks and q12w ±1 week until disease progression (up to maximum of 12 months)
To assess the efficacy of durvalumab treatment in terms of DoR. DoR is defined as the time from the date of first documented response per RECIST1.1 until the first date of documented progression per RECIST1.1 or death in the absence of disease progression
From 8 weeks ±1 week after IP treatment initiation and continue q8w ±1 week through 48 weeks and q12w ±1 week until disease progression (up to maximum of 12 months)
Number of participants with lung cancer mortality
Time Frame: From date of treatment start until death due to lung cancer (up to maximum of 12 months)
To assess the efficacy of durvalumab treatment in terms of lung cancer mortality
From date of treatment start until death due to lung cancer (up to maximum of 12 months)
Number of participants with adverse events, serious adverse events, adverse event of special interests, and immune-mediated adverse event
Time Frame: From screening (Day -28) till final visit (up to a maximum of 12 months)
To assess the safety and tolerability profile of durvalumab treatment
From screening (Day -28) till final visit (up to a maximum of 12 months)
Number of participants with abnormal physical examinations
Time Frame: At screening
To assess the safety and tolerability profile of durvalumab treatment
At screening
Number of participants with abnormal blood pressure
Time Frame: From screening (Day -28) till final visit (up to a maximum of 12 months
To assess the safety and tolerability profile of durvalumab treatment
From screening (Day -28) till final visit (up to a maximum of 12 months
Number of participants with abnormal pulse
Time Frame: From screening (Day -28) till final visit (up to a maximum of 12 months)
To assess the safety and tolerability profile of durvalumab treatment
From screening (Day -28) till final visit (up to a maximum of 12 months)
Number of participants with abnormal electrocardiograms
Time Frame: From screening (Day -28) till final visit (up to a maximum of 12 months)
To assess the safety and tolerability profile of durvalumab treatment
From screening (Day -28) till final visit (up to a maximum of 12 months)
Number of participants with abnormal clinical chemistry
Time Frame: From screening (Day -28) till final visit (up to a maximum of 12 months)
To assess the safety and tolerability profile of durvalumab treatment
From screening (Day -28) till final visit (up to a maximum of 12 months)
Number of participants with abnormal hematology
Time Frame: From screening (Day -28) till final visit (up to a maximum of 12 months
To assess the safety and tolerability profile of durvalumab treatment
From screening (Day -28) till final visit (up to a maximum of 12 months
Number of participants with abnormal urinalysis
Time Frame: From screening (Day -28) till final visit (up to a maximum of 12 months
To assess the safety and tolerability profile of durvalumab treatment
From screening (Day -28) till final visit (up to a maximum of 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Dr Andrea Riccardo Filippi, Fondazione IRCCS Policlinico San Matteo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 26, 2020

Primary Completion (Actual)

March 30, 2023

Study Completion (Actual)

December 5, 2023

Study Registration Dates

First Submitted

January 29, 2020

First Submitted That Met QC Criteria

January 29, 2020

First Posted (Actual)

January 30, 2020

Study Record Updates

Last Update Posted (Estimated)

January 8, 2024

Last Update Submitted That Met QC Criteria

January 5, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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