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ADRIATIC: Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation Therapy

Sponsor
AstraZeneca (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03703297
Collaborator
(none)
730
Enrollment
186
Locations
3
Arms
78.9
Anticipated Duration (Months)
3.9
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
730 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
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)
Actual Study Start Date :
Sep 27, 2018
Anticipated Primary Completion Date :
May 10, 2024
Anticipated Study Completion Date :
Apr 23, 2025

Arms and Interventions

Arm Intervention/Treatment
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.

Drug: Durvalumab
Durvalumab IV (intravenous infusion)
Other Names:
  • MEDI4736

    • Other: Placebo
    Placebo IV (intravenous infusion)
    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.

    Drug: Durvalumab
    Durvalumab IV (intravenous infusion)
    Other Names:
  • MEDI4736

    • Drug: Tremelimumab
    Tremelimumab IV (intravenous infusion)
    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.

    Other: Placebo
    Placebo IV (intravenous infusion)

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free survival (PFS) [Approximately 4 years]

      To assess the efficacy of Durvalumab monotherapy vs Placebo in terms of PFS

    2. Overall Survival (OS) [Approximately 6 years]

      To assess the efficacy of Durvalumab monotherapy vs Placebo in terms of OS

    Secondary Outcome Measures

    1. Overall Survival (OS) [Approximately 6 years]

      To assess the efficacy of Durvalumab & Tremelimumab combination therapy vs Placebo in terms of OS

    2. Objective Response Rate (ORR) [Approximately 6 years]

    3. Progression-free survival PFS [Approximately 4 years]

      To assess the efficacy of durvalumab and tremelimumab combination therapy compared to placebo in terms of PFS

    4. Progression-free survival at 18 months (PFS18) [Approximately 4 years]

    5. Progression-free survival at 24 months (PFS24) [Approximately 4 years]

    6. Time to death or distant metastasis (TTDM) [Approximately 6 years]

    7. Proportion of patients alive at 24 months (OS24) [Approximately 6 years]

    8. Proportion of patients alive at and 36 months (OS36) [Approximately 6 years]

    9. Time from randomization to second progression (PFS2) [Approximately 6 years]

    10. 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 [Approximately 6 years]

    11. To assess the PK of durvalumab and tremelimumab in blood (peak trough concentration) [Approximately 6 years]

    12. Presence of anti-drug antibodies (ADA) for durvalumab and tremelimumab (confirmatory results: positive or negative) [Approximately 6 years]

    13. PD-L1 expression in tumor and/or immune cells relative to response/efficacy outcomes (PFS, OS & ORR). [Approximately 6 years]

      To investigate the relationship between PDL1 expression & spatial distribution with Durva (mono) therapy & Durva+Treme (combination) therapy

    14. 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 [Approximately 6 years]

    Other Outcome Measures

    1. Adverse Events [Approximately 6 years]

    Eligibility Criteria

    Criteria

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Tucson Arizona United States 85715
    2 Research Site Santa Rosa California United States 95403
    3 Research Site New Haven Connecticut United States 06510
    4 Research Site Fort Myers Florida United States 33901
    5 Research Site Orange City Florida United States 32763
    6 Research Site Saint Petersburg Florida United States 33705
    7 Research Site Marietta Georgia United States 30060
    8 Research Site Hines Illinois United States 60141
    9 Research Site Fort Wayne Indiana United States 46804
    10 Research Site Muncie Indiana United States 47303
    11 Research Site Lexington Kentucky United States 40536
    12 Research Site Annapolis Maryland United States 21401
    13 Research Site Baltimore Maryland United States 21287
    14 Research Site Towson Maryland United States 21204
    15 Research Site Boston Massachusetts United States 02114
    16 Research Site Detroit Michigan United States 48201
    17 Research Site Grand Rapids Michigan United States 49503
    18 Research Site Minneapolis Minnesota United States 55407
    19 Research Site Summit New Jersey United States 07902
    20 Research Site New Hyde Park New York United States 11042
    21 Research Site Chapel Hill North Carolina United States 27599
    22 Research Site Portland Oregon United States 97239
    23 Research Site Philadelphia Pennsylvania United States 19111
    24 Research Site Pittsburgh Pennsylvania United States 15212
    25 Research Site Sioux Falls South Dakota United States 57104
    26 Research Site Chattanooga Tennessee United States 37404
    27 Research Site Nashville Tennessee United States 37203
    28 Research Site Nashville Tennessee United States 37232
    29 Research Site Dallas Texas United States 75390
    30 Research Site Kennewick Washington United States 99336
    31 Research Site Tacoma Washington United States 98405
    32 Research Site Charleston West Virginia United States 25304
    33 Research Site Huntington West Virginia United States 25701
    34 Research Site Milwaukee Wisconsin United States 53226
    35 Research Site Caba Argentina C1012AAR
    36 Research Site Caba Argentina C1280AEB
    37 Research Site Ciudadela Argentina 1702
    38 Research Site Córdoba Argentina X5004BAL
    39 Research Site La Plata Argentina 1900
    40 Research Site Mar del Plata Argentina 7600
    41 Research Site Rosario Argentina 2000
    42 Research Site San Salvador de Jujuy Argentina 4600
    43 Research Site Aalst Belgium 9300
    44 Research Site Anderlecht Belgium 1070
    45 Research Site Bruxelles Belgium 1200
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    47 Research Site Roeselare Belgium 8800
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    49 Research Site Toronto CA Canada M5G 2M9
    50 Research Site Winnipeg Manitoba Canada R3E 0V9
    51 Research Site Hamilton Ontario Canada L8V 5C2
    52 Research Site London Ontario Canada N6A 5W9
    53 Research Site Ottawa Ontario Canada K1H 8L6
    54 Research Site Toronto Ontario Canada M4N 3M5
    55 Research Site Montreal Quebec Canada H4A 3J1
    56 Research Site Beijing China 100021
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    58 Research Site Beijing China 100142
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    60 Research Site Beijing China 100730
    61 Research Site Bengbu China 233060
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    63 Research Site Changsha China 410013
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    65 Research Site Chongqing China 400030
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    67 Research Site Fuzhou China 350011
    68 Research Site Hangzhou China 310003
    69 Research Site Hefei China 230601
    70 Research Site Shanghai China 200030
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    72 Research Site Shenyang China 110001
    73 Research Site Shenyang China 110042
    74 Research Site Tianjin China 300060
    75 Research Site Wuhan China 430010
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    77 Research Site Wuhan China 430030
    78 Research Site Yangzhou China 225001
    79 Research Site Zhengzhou China 450008
    80 Research Site Brno Czechia 639 00
    81 Research Site Olomouc Czechia 775 21
    82 Research Site Ostrava Czechia 703 00
    83 Research Site Praha 2 Czechia 128 08
    84 Research Site Praha Czechia 140 59
    85 Research Site Berlin Germany 12351
    86 Research Site Freiburg Germany 79106
    87 Research Site Gauting Germany 82131
    88 Research Site Gerlingen Germany 70839
    89 Research Site Heidelberg Germany 69126
    90 Research Site Köln Germany 51109
    91 Research Site Mainz Germany 55131
    92 Research Site Münster Germany 48149
    93 Research Site Oldenburg Germany 26121
    94 Research Site Regensburg Germany 93053
    95 Research Site Wuerzburg Germany 97080
    96 Research Site Bangalore India 560068
    97 Research Site Bengaluru India 560076
    98 Research Site Gurgaon India 122001
    99 Research Site Brescia Italy 25123
    100 Research Site Milano Italy 20133
    101 Research Site Milano Italy 20141
    102 Research Site Orbassano Italy 10043
    103 Research Site Parma Italy 43126
    104 Research Site Roma Italy 00100
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    106 Research Site Terni Italy 05100
    107 Research Site Bunkyo-ku Japan 160-0023
    108 Research Site Chuo-ku Japan 104-0045
    109 Research Site Fukuoka-shi Japan 812-8582
    110 Research Site Iwakuni-shi Japan 740-8510
    111 Research Site Kashiwa Japan 277-8577
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    113 Research Site Kurume-shi Japan 830-0011
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    117 Research Site Osakasayama Japan 589-8511
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    119 Research Site Sapporo-shi Japan 003-0804
    120 Research Site Sendai-shi Japan 980-0873
    121 Research Site Sunto-gun Japan 411-8777
    122 Research Site Tokushima-shi Japan 770-8503
    123 Research Site Ube-shi Japan 755-0241
    124 Research Site Changwon-si Korea, Republic of 51353
    125 Research Site Cheongju-si Korea, Republic of 28644
    126 Research Site Daegu Korea, Republic of 42415
    127 Research Site Goyang-si Korea, Republic of 10408
    128 Research Site Gyeongsangnam-do Korea, Republic of 52727
    129 Research Site Seongnam-si Korea, Republic of 13620
    130 Research Site Seoul Korea, Republic of 03080
    131 Research Site Seoul Korea, Republic of 03722
    132 Research Site Seoul Korea, Republic of 05505
    133 Research Site Suwon-si Korea, Republic of 16499
    134 Research Site Amsterdam Netherlands 1081 HV
    135 Research Site Den Bosch Netherlands 5223 GZ
    136 Research Site Groningen Netherlands 9713 GZ
    137 Research Site Harderwijk Netherlands 3844 DG
    138 Research Site Hengelo Netherlands 7555 DL
    139 Research Site Gdańsk Poland 80-214
    140 Research Site Olsztyn Poland 10-357
    141 Research Site Poznań Poland 60-569
    142 Research Site Tomaszów Mazowiecki Poland 97-200
    143 Research Site Warszawa Poland 02-781
    144 Research Site Wroclaw Poland 53-413
    145 Research Site Kazan Russian Federation 420029
    146 Research Site Kirov Russian Federation 610021
    147 Research Site Moscow Russian Federation 105229
    148 Research Site Moscow Russian Federation 115478
    149 Research Site Moscow Russian Federation 125284
    150 Research Site Obninsk Russian Federation 249036
    151 Research Site Omsk Russian Federation 644013
    152 Research Site Ufa Russian Federation 450054
    153 Research Site Volgograd Russian Federation 400138
    154 Research Site Barcelona Spain 08003
    155 Research Site Barcelona Spain 08035
    156 Research Site Madrid Spain 28034
    157 Research Site Madrid Spain 28040
    158 Research Site Madrid Spain 28041
    159 Research Site Oviedo Spain 33011
    160 Research Site Sevilla Spain 41013
    161 Research Site Valencia Spain 46026
    162 Research Site Zaragoza Spain 50009
    163 Research Site Hsinchu Taiwan 300
    164 Research Site Kaohsiung City Taiwan 83301
    165 Research Site Keelung City Taiwan 20445
    166 Research Site Taichung Taiwan 40705
    167 Research Site Tainan City Taiwan 70403
    168 Research Site Tainan Taiwan 736
    169 Research Site Taipei Taiwan 112
    170 Research Site Taipei Taiwan 235
    171 Research Site Taoyuan City Taiwan 333
    172 Research Site Yunlin Taiwan 640
    173 Research Site Adana Turkey 01060
    174 Research Site Ankara Turkey 06230
    175 Research Site Ankara Turkey 06280
    176 Research Site Antalya Turkey 07059
    177 Research Site Edirne Turkey 22030
    178 Research Site Istanbul Turkey 34030
    179 Research Site Izmir Turkey 35620
    180 Research Site Konya Turkey 42080
    181 Research Site Samsun Turkey
    182 Research Site Manchester United Kingdom M20 4BX
    183 Research Site Truro United Kingdom TR1 3LJ
    184 Research Site Hanoi Vietnam 100000
    185 Research Site Ho Chi Minh Vietnam 700000
    186 Research Site Ho Chi Minh Vietnam 70000

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    • Study Director: Haiyi Jiang, M.D., AstraZeneca

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT03703297
    Other Study ID Numbers:
    • D933QC00001
    First Posted:
    Oct 11, 2018
    Last Update Posted:
    Jun 8, 2022
    Last Verified:
    Jun 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
    Keywords provided by AstraZeneca
    Small Cell Lung Cancer
    SCLC
    LS-SCLC
    Limited Stage
    Carcinoma
    Lung Cancer
    Additional relevant MeSH terms:
    Lung Neoplasms
    Small Cell Lung Carcinoma
    Durvalumab
    Tremelimumab

    Study Results

    No Results Posted as of Jun 8, 2022