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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02352948




Registration number
NCT02352948
Ethics application status
Date submitted
28/01/2015
Date registered
2/02/2015

Titles & IDs
Public title
A Global Study to Assess the Effects of MEDI4736 (Durvalumab), Given as Monotherapy or in Combination With Tremelimumab Determined by PD-L1 Expression Versus Standard of Care in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer
Scientific title
A Phase III, Open Label, Randomised, Multi-centre, International Study of MEDI4736, Given as Monotherapy or in Combination With Tremelimumab Determined by PD-L1 Expression Versus Standard of Care in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Stage IIIB-IV) Who Have Received at Least Two Prior Systemic Treatment Regimens Including One Platinum Based Chemotherapy Regimen and Do Not Have Known EGFR TK Activating Mutations or ALK Rearrangements (ARCTIC).
Secondary ID [1] 0 0
2014-000338-46
Secondary ID [2] 0 0
D4191C00004
Universal Trial Number (UTN)
Trial acronym
ARCTIC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non - Small Cell Lung Cancer NSCLC 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MEDI4736 (durvalumab)
Treatment: Drugs - Vinorelbine
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Erlotinib
Treatment: Drugs - MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4)
Treatment: Drugs - tremelimumab (anti-CTLA4)

Experimental: MEDI4736 (durvalumab) monotherapy in Sub-study A - MEDI4736 (durvalumab) by intravenous infusion. Sub-study A for patients with PD-L1 positive tumors.

Active comparator: Standard of Care in Sub-study A - Investigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study A for patients with PD-L1 positive tumors.

Experimental: MEDI4736 (durvalumab) + tremelimumab in Sub-study B - MEDI4736 (durvalumab) by intravenous infusion and tremelimumab by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.

Active comparator: Standard of Care in Sub-study B - Investigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study B for patients with PD-L1 negative tumors.

Experimental: MEDI4736 (durvalumab) monotherapy in Sub-study B - MEDI4736 (durvalumab) by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.

Experimental: tremelimumab in Sub-study B - tremelimumab by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.


Treatment: Drugs: MEDI4736 (durvalumab)
MEDI4736 (durvalumab) treatment by intravenous infusion

Treatment: Drugs: Vinorelbine
Vinorelbine by intravenous infusion. Administered at a dose of 30 mg/m2 iv on Days 1, 8, 15 and 22 of a 28-day cycle.

Treatment: Drugs: Gemcitabine
Gemcitabine by intravenous infusion. Administered at a dose of 1000 mg/m2 iv over 30 minutes on Days 1, 8, and 15 of a 28-day cycle.

Treatment: Drugs: Erlotinib
Erlotinib administered at a dose of 150 mg once daily as a tablet for oral administration

Treatment: Drugs: MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4)
MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4) treatment by intravenous infusion

Treatment: Drugs: tremelimumab (anti-CTLA4)
tremelimumab (anti-CTLA4) treatment by intravenous infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From randomization (Day 1) until death due to any cause, approximately 36 months
Primary outcome [2] 0 0
Progression-Free Survival (PFS)
Timepoint [2] 0 0
Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed up to a maximum of approximately 3 years.
Secondary outcome [1] 0 0
OS, Contribution of the Components Analysis of Sub-study B
Timepoint [1] 0 0
From randomization (Day 1) until death due to any cause, approximately 36 months
Secondary outcome [2] 0 0
Percentage of Participants Alive at 12 Months (OS12)
Timepoint [2] 0 0
From randomization (Day 1) up to 12 months
Secondary outcome [3] 0 0
PFS, Contribution of the Components Analysis of Sub-study B
Timepoint [3] 0 0
Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed up to a maximum of approximately 3 years.
Secondary outcome [4] 0 0
Objective Response Rate (ORR)
Timepoint [4] 0 0
Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed up to a maximum of approximately 3 years.
Secondary outcome [5] 0 0
Duration of Response (DoR)
Timepoint [5] 0 0
Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed up to a maximum of approximately 3 years.
Secondary outcome [6] 0 0
Percentage of Participants Alive and Progression Free at 6 Months (APF6)
Timepoint [6] 0 0
Tumour scans performed at baseline then every ~8 weeks up to 6 months
Secondary outcome [7] 0 0
Percentage of Participants Alive and Progression Free at 12 Months (APF12)
Timepoint [7] 0 0
Tumour scans performed at baseline then every ~8 weeks up to 12 months.
Secondary outcome [8] 0 0
Time From Randomisation to Second Progression (PFS2) of Sub-study B
Timepoint [8] 0 0
Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until first progression. Disease then assessed per local practice until 2nd progression. Assessed up to a maximum of approximately 3 years.

Eligibility
Key inclusion criteria
* Aged at least 18 years
* Documented evidence of NSCLC (Stage IIIB/ IV disease)
* Disease progression or recurrence after both a platinum-based chemotherapy regimen and at least 1 additional regimen for treatment of NSCLC
* World Health Organization (WHO) Performance Status of 0 or 1
* Estimated life expectancy more than 12 weeks
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior exposure to any anti-PD-1 or anti-PD-L1 antibody or anti-CTLA4
* Brain metastases or spinal cord compression unless asymptomatic, treated and stable (not requiring steroids)
* Active or prior documented autoimmune disease within the past 2 years
* Evidence of severe or uncontrolled systemic disease, including active bleeding diatheses or active infections including hepatitis B, C and HIV
* Any unresolved toxicity CTCAE (Common Terminology Criteria of Adverse Events) >Grade 2 from previous anti-cancer therapy
* Known EGFR TK activating mutations or ALK rearrangements
* Any prior Grade =3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1
* Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/01/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/08/2023
Sample size
Target
Accrual to date
Final
597
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Murdoch
Recruitment hospital [2] 0 0
Research Site - Port Macquarie
Recruitment postcode(s) [1] 0 0
6150 - Murdoch
Recruitment postcode(s) [2] 0 0
2444 - Port Macquarie
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
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California
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Colorado
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Florida
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Georgia
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Kentucky
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Maryland
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Michigan
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Missouri
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Nebraska
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New York
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North Carolina
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Ohio
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Tennessee
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Washington
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Charleroi
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Gent
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Santiago
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Temuco
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Nova Ves pod Plesi
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Praha 2
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Avignon Cedex 9
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Löwenstein
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Regensburg
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Trier
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Ulm
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Villingen-Schwenningen
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Greece
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Athens
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Greece
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Thessaloniki
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Hong Kong
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Miskolc
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Törökbálint
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Zalaegerszeg
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Tel Hashomer
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Aviano
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Candiolo
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Catania
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Rimini
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Terni
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Kanazawa
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Kobe-shi
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Kurume-shi
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Matsuyama-shi
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Nagoya-shi
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Okayama-shi
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Japan
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Osaka-shi
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Japan
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Osakasayama
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Japan
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Sakai-shi
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Sapporo-shi
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Sendai-shi
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Japan
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Shinjuku-ku
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Japan
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Sunto-gun
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Japan
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Takatsuki-shi
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Japan
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Wakayama-shi
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Japan
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Yokohama-shi
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Korea, Republic of
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Busan
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Cheongju-si
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Korea, Republic of
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Incheon
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Korea, Republic of
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Jeonnam
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Korea, Republic of
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Seongnam-si
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Korea, Republic of
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Seoul
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Netherlands
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Amsterdam
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Poland
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Lublin
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Poland
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Poznan
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Poland
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Warszawa
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Romania
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Alba Iulia
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Baia Mare
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Cluj Napoca
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Romania
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Cluj-Napoca
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Romania
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Onesti
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Romania
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Oradea
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Romania
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Timisoara
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Russian Federation
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Arkhangelsk
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Russian Federation
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Omsk
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Russian Federation
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Saint Petersburg
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Russian Federation
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St. Petersburg
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Serbia
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Belgrade
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Serbia
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Belgrad
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Serbia
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Gornji Matejevac
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Serbia
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Kragujevac
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Serbia
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Sremska Kamenica
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Singapore
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Singapore
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Spain
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A Coruña
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Spain
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Alicante
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Spain
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Barcelona
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Spain
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Girona
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Spain
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Jaén
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Spain
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Lleida
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Spain
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Madrid
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Spain
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San Sebastian
Country [138] 0 0
Spain
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Sevilla
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Spain
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Valencia
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Taiwan
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Taichung
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Taiwan
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Tainan
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Taiwan
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Taipei City
Country [143] 0 0
Taiwan
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Taipei
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Thailand
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Bangkok
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Thailand
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Muang
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Thailand
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Phitsanulok
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Thailand
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Songkla
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United Kingdom
State/province [148] 0 0
Birmingham
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United Kingdom
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London
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United Kingdom
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Southampton
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United Kingdom
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Stevenage
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United Kingdom
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Truro
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United Kingdom
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Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Paul Stockman, MBChB, PhD
Address 0 0
AstraZeneca
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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 document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
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
Available to whom?
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
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02352948