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

Sponsor
AstraZeneca (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04249362
Collaborator
(none)
150
53
2
36.1
2.8
0.1

Study Details

Study Description

Brief Summary

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])

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
150 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Nov 26, 2020
Anticipated Primary Completion Date :
Nov 21, 2022
Anticipated Study Completion Date :
Nov 30, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort A

Patients received standard radiotherapy [60 gray (Gy) ± 10% or hypofractionated BED] prior to study entry.

Drug: Durvalumab
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.

    Drug: Durvalumab
    All patients will receive 1500 mg durvalumab via IV infusion q4w for up to a maximum of 12 months.
    Other Names:
  • MEDI4736
  • Outcome Measures

    Primary Outcome Measures

    1. Number of participants with Grade 3 and Grade 4 possibly-related adverse events (PRAEs) [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

    Secondary Outcome Measures

    1. Median Progression-free survival (PFS) [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

    2. PFS at 6 months (PFS6) [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

    3. PFS at 12 months (PFS12) [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

    4. Median overall survival (OS) [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

    5. OS at 12 months (OS12) [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

    6. Objective response rate (ORR) [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

    7. Duration of response (DoR) [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

    8. Number of participants with lung cancer mortality [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

    9. Number of participants with adverse events, serious adverse events, adverse event of special interests, and immune-mediated adverse event [From screening (Day -28) till final visit (up to a maximum of 12 months)]

      To assess the safety and tolerability profile of durvalumab treatment

    10. Number of participants with abnormal physical examinations [At screening]

      To assess the safety and tolerability profile of durvalumab treatment

    11. Number of participants with abnormal blood pressure [From screening (Day -28) till final visit (up to a maximum of 12 months]

      To assess the safety and tolerability profile of durvalumab treatment

    12. Number of participants with abnormal pulse [From screening (Day -28) till final visit (up to a maximum of 12 months)]

      To assess the safety and tolerability profile of durvalumab treatment

    13. Number of participants with abnormal electrocardiograms [From screening (Day -28) till final visit (up to a maximum of 12 months)]

      To assess the safety and tolerability profile of durvalumab treatment

    14. Number of participants with abnormal clinical chemistry [From screening (Day -28) till final visit (up to a maximum of 12 months)]

      To assess the safety and tolerability profile of durvalumab treatment

    15. Number of participants with abnormal hematology [From screening (Day -28) till final visit (up to a maximum of 12 months]

      To assess the safety and tolerability profile of durvalumab treatment

    16. Number of participants with abnormal urinalysis [From screening (Day -28) till final visit (up to a maximum of 12 months]

      To assess the safety and tolerability profile of durvalumab treatment

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 130 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    1. Life expectancy of greater than 12 weeks.

    2. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Tucson Arizona United States 85704
    2 Research Site Tampa Florida United States 33612
    3 Research Site Royal Oak Michigan United States 48073
    4 Research Site Tacoma Washington United States 98405
    5 Research Site Bayonne France 64100
    6 Research Site Limoges France 87000
    7 Research Site Lyon Cedex 08 France 69373
    8 Research Site Marseille France 13009
    9 Research Site Montpellier France 34070
    10 Research Site Nimes France 30029
    11 Research Site Rouen France 76031
    12 Research Site Vantoux France 57070
    13 Research Site Ancona Italy 60126
    14 Research Site Brescia Italy 25100
    15 Research Site Firenze Italy 50134
    16 Research Site Genova Italy 16132
    17 Research Site Meldola Italy 47014
    18 Research Site Messina Italy 98158
    19 Research Site Modena Italy 41124
    20 Research Site Monza Italy 20900
    21 Research Site Negrar Italy 37024
    22 Research Site Pavia Italy 27100
    23 Research Site Pisa Italy 56124
    24 Research Site Ravenna Italy 48121
    25 Research Site Roma Italy 00128
    26 Research Site Białystok Poland 15-044
    27 Research Site Gdańsk Poland 80-214
    28 Research Site Koszalin Poland 75-581
    29 Research Site Olsztyn Poland 10-228
    30 Research Site Skorzewo Poland 60-185
    31 Research Site Szczecin Poland 71-730
    32 Research Site Warszawa Poland 02-781
    33 Research Site Wroclaw Poland 53-413
    34 Research Site Barnaul Russian Federation 656049
    35 Research Site Kazan Russian Federation 420029
    36 Research Site Nizhny Novgorod Russian Federation 603081
    37 Research Site Orenburg Russian Federation 460021
    38 Research Site St. Petersburg Russian Federation 197002
    39 Research Site St. Petersburg Russian Federation 197758
    40 Research Site St.Petersburg Russian Federation 191014
    41 Research Site Ufa Russian Federation 450054
    42 Research Site Yaroslavl Russian Federation 150054
    43 Research Site A Coruña Spain 15006
    44 Research Site Barcelona Spain 8035
    45 Research Site Castello de la Plana Spain 12002
    46 Research Site Madrid Spain 28007
    47 Research Site Madrid Spain 28040
    48 Research Site Madrid Spain 28050
    49 Research Site Oviedo Spain 33011
    50 Research Site Pamplona Spain 31008
    51 Research Site Sabadell(Barcelona) Spain 08208
    52 Research Site Sevilla Spain 41013
    53 Research Site Valencia Spain 46015

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT04249362
    Other Study ID Numbers:
    • D4194C00009
    First Posted:
    Jan 30, 2020
    Last Update Posted:
    Aug 23, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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
    Keywords provided by AstraZeneca
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 23, 2022