Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04249362
Recruitment Status : Not yet recruiting
First Posted : January 30, 2020
Last Update Posted : September 25, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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
Non-small Cell Lung Cancer Drug: Durvalumab 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)

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: N/A
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
Estimated Study Start Date : December 1, 2020
Estimated Primary Completion Date : November 30, 2023
Estimated Study Completion Date : November 30, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

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 Name: 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 Name: MEDI4736




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. Number of participants with abnormal physical examinations [ Time Frame: At screening ]
    To assess the safety and tolerability profile of durvalumab treatment

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04249362


Contacts
Layout table for location contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
Layout table for location information
United States, Arizona
Research Site
Tucson, Arizona, United States, 85704
United States, Washington
Research Site
Tacoma, Washington, United States, 98405
France
Research Site
Limoges, France, 87000
Research Site
Lyon Cedex 08, France, 69373
Research Site
Vantoux, France, 57070
Italy
Research Site
Ancona, Italy, 60126
Research Site
Firenze, Italy, 50134
Research Site
Meldola, Italy, 47014
Research Site
Messina, Italy, 98158
Research Site
Modena, Italy, 41124
Research Site
Monza, Italy, 20900
Research Site
Pavia, Italy, 27100
Research Site
Pisa, Italy, 56124
Research Site
Ravenna, Italy, 48121
Poland
Research Site
Białystok, Poland, 15-044
Research Site
Gdańsk, Poland, 80-214
Research Site
Warszawa, Poland, 02-781
Spain
Research Site
A Coruña, Spain, 15006
Research Site
Barcelona, Spain, 8035
Research Site
Castello de la Plana, Spain, 12002
Research Site
Madrid, Spain, 28007
Research Site
Oviedo, Spain, 33011
Research Site
Sabadell(Barcelona), Spain, 08208
Research Site
Valencia, Spain, 46015
Sponsors and Collaborators
AstraZeneca
Investigators
Layout table for investigator information
Principal Investigator: Dr Andrea Riccardo Filippi Fondazione IRCCS Policlinico San Matteo
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04249362    
Other Study ID Numbers: D4194C00009
First Posted: January 30, 2020    Key Record Dates
Last Update Posted: September 25, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
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.
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.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

Layout table for additional information
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:
Radiation therapy
Phase II
Palliative Radiotherapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Durvalumab
Antineoplastic Agents, Immunological
Antineoplastic Agents