Clinical trial NCT03703297: 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: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Small Cell Lung Cancer
Keywords: Small Cell Lung Cancer
SCLC
LS-SCLC
Limited Stage
Carcinoma
Lung Cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2018-10-11
Enrollment: 730
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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)

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Approximately 6 years
measure: Overall Survival (OS)
timeFrame: Approximately 6 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Approximately 6 years
measure: Objective Response Rate (ORR)
timeFrame: Approximately 6 years
measure: Progression-free survival PFS
timeFrame: Approximately 6 years
measure: Progression-free survival at 18 months (PFS18)
timeFrame: Approximately 6 years
measure: Progression-free survival at 24 months (PFS24)
timeFrame: Approximately 6 years
measure: Time to death or distant metastasis (TTDM)
timeFrame: Approximately 6 years
measure: Proportion of patients alive at 24 months (OS24)
timeFrame: Approximately 6 years
measure: Proportion of patients alive at and 36 months (OS36)
timeFrame: Approximately 6 years
measure: Time from randomization to second progression (PFS2)
timeFrame: Approximately 6 years
measure: 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
timeFrame: Approximately 6 years
measure: To assess the PK of durvalumab and tremelimumab in blood (peak trough concentration)
timeFrame: Approximately 6 years
measure: Presence of anti-drug antibodies (ADA) for durvalumab and tremelimumab (confirmatory results: positive or negative)
timeFrame: Approximately 6 years
measure: PD-L1 expression in tumor and/or immune cells relative to response/efficacy outcomes (PFS, OS & ORR).
timeFrame: Approximately 6 years
measure: 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
timeFrame: Approximately 6 years
Other outcomes:
measure: Adverse Events
timeFrame: Approximately 6 years
Locations:
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Santa Rosa
country: United States
facility: Research Site
state: California
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Fort Myers
country: United States
facility: Research Site
state: Florida
city: Orange City
country: United States
facility: Research Site
state: Florida
city: Saint Petersburg
country: United States
facility: Research Site
state: Florida
city: Marietta
country: United States
facility: Research Site
state: Georgia
city: Hines
country: United States
facility: Research Site
state: Illinois
city: Fort Wayne
country: United States
facility: Research Site
state: Indiana
city: Muncie
country: United States
facility: Research Site
state: Indiana
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Annapolis
country: United States
facility: Research Site
state: Maryland
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Towson
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Grand Rapids
country: United States
facility: Research Site
state: Michigan
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Summit
country: United States
facility: Research Site
state: New Jersey
city: New Hyde Park
country: United States
facility: Research Site
state: New York
city: Chapel Hill
country: United States
facility: Research Site
state: North Carolina
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Research Site
state: South Dakota
city: Chattanooga
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Kennewick
country: United States
facility: Research Site
state: Washington
city: Tacoma
country: United States
facility: Research Site
state: Washington
city: Charleston
country: United States
facility: Research Site
state: West Virginia
city: Huntington
country: United States
facility: Research Site
state: West Virginia
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: Caba
country: Argentina
facility: Research Site
city: Caba
country: Argentina
facility: Research Site
city: Córdoba
country: Argentina
facility: Research Site
city: Mar del Plata
country: Argentina
facility: Research Site
city: Rosario
country: Argentina
facility: Research Site
city: Aalst
country: Belgium
facility: Research Site
city: Anderlecht
country: Belgium
facility: Research Site
city: Bruxelles
country: Belgium
facility: Research Site
city: Hasselt
country: Belgium
facility: Research Site
city: Roeselare
country: Belgium
facility: Research Site
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Toronto
country: Canada
facility: Research Site
state: CA
city: Winnipeg
country: Canada
facility: Research Site
state: Manitoba
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: London
country: Canada
facility: Research Site
state: Ontario
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Bengbu
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Fuzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Yangzhou
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Olomouc
country: Czechia
facility: Research Site
city: Ostrava
country: Czechia
facility: Research Site
city: Praha 2
country: Czechia
facility: Research Site
city: Praha
country: Czechia
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Freiburg
country: Germany
facility: Research Site
city: Gauting
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: Mainz
country: Germany
facility: Research Site
city: Münster
country: Germany
facility: Research Site
city: Oldenburg
country: Germany
facility: Research Site
city: Regensburg
country: Germany
facility: Research Site
city: Stuttgart
country: Germany
facility: Research Site
city: Wuerzburg
country: Germany
facility: Research Site
city: Bengaluru
country: India
facility: Research Site
city: Gurgaon
country: India
facility: Research Site
city: Brescia
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Orbassano
country: Italy
facility: Research Site
city: Parma
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Rozzano
country: Italy
facility: Research Site
city: Terni
country: Italy
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Iwakuni-shi
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Kurume-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Niigata-shi
country: Japan
facility: Research Site
city: Osakasayama
country: Japan
facility: Research Site
city: Sakai-shi
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Sendai-shi
country: Japan
facility: Research Site
city: Sunto-gun
country: Japan
facility: Research Site
city: Tokushima-shi
country: Japan
facility: Research Site
city: Ube-shi
country: Japan
facility: Research Site
city: Changwon-si
country: Korea, Republic of
facility: Research Site
city: Cheongju-si
country: Korea, Republic of
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Jinju-si
country: Korea, Republic of
facility: Research Site
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon-si
country: Korea, Republic of
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Den Bosch
country: Netherlands
facility: Research Site
city: Groningen
country: Netherlands
facility: Research Site
city: Harderwijk
country: Netherlands
facility: Research Site
city: Hengelo
country: Netherlands
facility: Research Site
city: Gdańsk
country: Poland
facility: Research Site
city: Olsztyn
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Tomaszów Mazowiecki
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Kazan
country: Russian Federation
facility: Research Site
city: Kirov
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Obninsk
country: Russian Federation
facility: Research Site
city: Omsk
country: Russian Federation
facility: Research Site
city: Ufa
country: Russian Federation
facility: Research Site
city: Volgograd
country: Russian Federation
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Oviedo
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Hsinchu
country: Taiwan
facility: Research Site
city: Kaohsiung City
country: Taiwan
facility: Research Site
city: Keelung City
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan City
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan City
country: Taiwan
facility: Research Site
city: Yunlin
country: Taiwan
facility: Research Site
city: Adana
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Antalya
country: Turkey
facility: Research Site
city: Edirne
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Konya
country: Turkey
facility: Research Site
city: Samsun
country: Turkey
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Truro
country: United Kingdom
facility: Research Site
city: Ha Noi
country: Vietnam
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Haiyi Jiang, M.D.
role: STUDY_DIRECTOR
References:
citation: 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.