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Trial record 1 of 1 for:    NCT03703297
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Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation Therapy (ADRIATIC)

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ClinicalTrials.gov Identifier: NCT03703297
Recruitment Status : Active, not recruiting
First Posted : October 11, 2018
Last Update Posted : September 17, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE September 19, 2018
First Posted Date  ICMJE October 11, 2018
Last Update Posted Date September 17, 2021
Actual Study Start Date  ICMJE September 27, 2018
Estimated Primary Completion Date May 10, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 17, 2020)
  • Progression-free survival (PFS) [ Time Frame: Approximately 4 years ]
    To assess the efficacy of Durvalumab monotherapy vs Placebo in terms of PFS
  • Overall Survival (OS) [ Time Frame: Approximately 6 years ]
    To assess the efficacy of Durvalumab monotherapy vs Placebo in terms of OS
Original Primary Outcome Measures  ICMJE
 (submitted: October 10, 2018)
  • Progression-free survival (PFS) [ Time Frame: Approximately 5 years ]
  • Overall Survival (OS) [ Time Frame: Approximately 5 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 17, 2020)
  • Overall Survival (OS) [ Time Frame: Approximately 6 years ]
    To assess the efficacy of Durvalumab & Tremelimumab combination therapy vs Placebo in terms of OS
  • Objective Response Rate (ORR) [ Time Frame: Approximately 6 years ]
  • Progression-free survival PFS [ Time Frame: Approximately 4 years ]
    To assess the efficacy of durvalumab and tremelimumab combination therapy compared to placebo in terms of PFS
  • Progression-free survival at 18 months (PFS18) [ Time Frame: Approximately 4 years ]
  • Progression-free survival at 24 months (PFS24) [ Time Frame: Approximately 4 years ]
  • Time to death or distant metastasis (TTDM) [ Time Frame: Approximately 6 years ]
  • Proportion of patients alive at 24 months (OS24) [ Time Frame: Approximately 6 years ]
  • Proportion of patients alive at and 36 months (OS36) [ Time Frame: Approximately 6 years ]
  • Time from randomization to second progression (PFS2) [ Time Frame: Approximately 6 years ]
  • To assess symptoms and health-related QoL in patients treated withdurvalumab or durvalumab and tremelimumab combination therapy compared to placebo using the EORTC QLQ-C30 v3 [ Time Frame: Approximately 6 years ]
  • To assess the PK of durvalumab and tremelimumab in blood (peak trough concentration) [ Time Frame: Approximately 6 years ]
  • Presence of anti-drug antibodies (ADA) for durvalumab and tremelimumab (confirmatory results: positive or negative) [ Time Frame: Approximately 6 years ]
  • PD-L1 expression in tumor and/or immune cells relative to response/efficacy outcomes (PFS, OS & ORR). [ Time Frame: Approximately 6 years ]
    To investigate the relationship between PDL1 expression & spatial distribution with Durva (mono) therapy & Durva+Treme (combination) therapy
  • To assess symptoms and health-related QoL in patients treated withdurvalumab or durvalumab and tremelimumab combination therapy compared to placebo using the EORTC QLQ-LC13 [ Time Frame: Approximately 6 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 10, 2018)
  • Overall Survival (OS) [ Time Frame: Approximately 5 years ]
  • Objective Response Rate (ORR) [ Time Frame: Approximately 5 years ]
  • Progression-free survival PFS [ Time Frame: Approximately 5 years ]
  • Progression-free survival at 18 months (PFS18) [ Time Frame: Approximately 5 years ]
  • Progression-free survival at 24 months (PFS24) [ Time Frame: Approximately 5 years ]
  • Time to death or distant metastasis (TTDM) [ Time Frame: Approximately 5 years ]
  • Proportion of patients alive at 24 months (OS24) [ Time Frame: Approximately 5 years ]
  • Proportion of patients alive at and 36 months (OS36) [ Time Frame: Approximately 5 years ]
  • Time from randomization to second progression (PFS2) [ Time Frame: Approximately 5 years ]
  • To assess symptoms and health-related QoL in patients treated withdurvalumab or durvalumab and tremelimumab combination therapy compared to placebo using the EORTC QLQ-C30 v3 [ Time Frame: Approximately 5 years ]
  • To assess the PK of durvalumab and tremelimumab in blood (peak trough concentration) [ Time Frame: Approximately 5 years ]
  • Presence of anti-drug antibodies (ADA) for durvalumab and tremelimumab (confirmatory results: positive or negative) [ Time Frame: Approximately 5 years ]
  • To assess a relationship between a tumor mutational burden (TMB) measured as biomarker presence in tumor and/or blood and Progression-free survival (PFS) with durvalumab and durvalumab and tremelimumab combination therapy [ Time Frame: Approximately 5 years ]
  • To assess symptoms and health-related QoL in patients treated withdurvalumab or durvalumab and tremelimumab combination therapy compared to placebo using the EORTC QLQ-LC13 [ Time Frame: Approximately 5 years ]
  • To assess a relationship between a tumor mutational burden (TMB) measured as biomarker presence in tumor and/or blood and Objective Response Rate (ORR) with durvalumab and durvalumab and tremelimumab combination therapy [ Time Frame: Approximately 5 years ]
  • To assess a relationship between a tumor mutational burden (TMB) measured as biomarker presence in tumor and/or blood and Overall Survival (OS) with durvalumab and durvalumab and tremelimumab combination therapy [ Time Frame: Approximately 5 years ]
Current Other Pre-specified Outcome Measures
 (submitted: November 17, 2020)
Adverse Events [ Time Frame: Approximately 6 years ]
Original Other Pre-specified Outcome Measures
 (submitted: October 10, 2018)
Adverse Events [ Time Frame: Approximately 5 years ]
 
Descriptive Information
Brief Title  ICMJE Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation Therapy
Official Title  ICMJE A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center, International Study of Durvalumab or Durvalumab and Tremelimumab as Consolidation Treatment for Patients With Limited Stage Small Cell Lung Cancer Who Have Not Progressed Following Concurrent Chemoradiation Therapy (ADRIATIC)
Brief Summary This is a Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center, International Study of Durvalumab or Durvalumab and Tremelimumab as Consolidation Treatment for Patients with LS-SCLC Who Have Not Progressed Following Concurrent Chemoradiation Therapy
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Durvalumab
    Durvalumab IV (intravenous infusion)
    Other Name: MEDI4736
  • Drug: Tremelimumab
    Tremelimumab IV (intravenous infusion)
  • Other: Placebo
    Placebo IV (intravenous infusion)
Study Arms  ICMJE
  • Experimental: Durvalumab + Placebo
    Durvalumab monotherapy: Durvalumab (1500 mg intravenous [IV]) q4w in combination with placebo saline solution (IV) q4w for up to 4 doses/cycles each, followed by durvalumab 1500 mg q4w. The first durvalumab monotherapy 1500 mg dose q4w will be 4 weeks after the final dose of durvalumab in combination with placebo saline solution.
    Interventions:
    • Drug: Durvalumab
    • Other: Placebo
  • Experimental: Durvalumab + Tremelimumab
    Durvalumab in combination with tremelimumab: Durvalumab (1500 mg IV) q4w in combination with tremelimumab (75 mg IV) q4w for up to 4 doses/cycles each, followed by durvalumab 1500 mg q4w. The first durvalumab monotherapy 1500 mg dose q4w will be 4 weeks after the final dose of durvalumab in combination with tremelimumab.
    Interventions:
    • Drug: Durvalumab
    • Drug: Tremelimumab
  • Placebo Comparator: Placebo + Placebo
    Placebo: Placebo saline solution (IV) q4w in combination with a second placebo saline solution (IV) q4w for up to 4 doses/cycles each, followed by a single placebo saline solution q4w. The first placebo saline solution monotherapy dose q4w will be 4 weeks after the final dose of the 2 placebo saline solutions in combination.
    Intervention: Other: Placebo
Publications * Senan S, Okamoto I, Lee GW, Chen Y, Niho S, Mak G, Yao W, Shire N, Jiang H, Cho BC. Design and Rationale for a Phase III, Randomized, Placebo-controlled Trial of Durvalumab With or Without Tremelimumab After Concurrent Chemoradiotherapy for Patients With Limited-stage Small-cell Lung Cancer: The ADRIATIC Study. Clin Lung Cancer. 2020 Mar;21(2):e84-e88. doi: 10.1016/j.cllc.2019.12.006. Epub 2019 Dec 28.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: November 17, 2020)
724
Original Estimated Enrollment  ICMJE
 (submitted: October 10, 2018)
600
Estimated Study Completion Date  ICMJE May 10, 2024
Estimated Primary Completion Date May 10, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  1. Histologically or cytologically documented limited-stage small cell lung cancer (stage I-III).
  2. Received 4 cycles of chemotherapy concurrent with radiotherapy, which must be completed within 1 to 42 days prior to randomization and the first dose of IP. Chemotherapy must contain platinum and IV etoposide. Radiotherapy must be either total 60-66 Gy over 6 weeks for the standard QD regimen or total 45 Gy over 3 weeks for hyperfractionated BD schedules.
  3. PCI may be delivered at the discretion of investigator and local standard of care, and must be conducted after the end of cCRT and completed between 1 to 42 days to first dose of IP.

4 .Have not progressed following definitive concurrent chemoradiation 5 .Life expectancy ≥ 12 weeks at Day 1. 6. ECOG 0 or 1 at enrolment.

Exclusion criteria:

  1. Extensive-stage SCLC
  2. Active or prior documented autoimmune or inflammatory disorders
  3. Uncontrolled intercurrent illness, including but not limited to interstitial lung disease.
  4. Active infection including tuberculosis, HIV, hepatitis B and C
  5. Patients who received sequential chemotherapy and radiotherapy (no overlap of RT with chemotherapy)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Belgium,   Canada,   China,   Czechia,   Germany,   India,   Italy,   Japan,   Korea, Republic of,   Mexico,   Netherlands,   Poland,   Russian Federation,   Spain,   Taiwan,   Turkey,   United Kingdom,   United States,   Vietnam
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03703297
Other Study ID Numbers  ICMJE D933QC00001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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.
Supporting Materials: Study Protocol
Supporting Materials: 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
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Haiyi Jiang, M.D. AstraZeneca
PRS Account AstraZeneca
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP