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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02684006




Registration number
NCT02684006
Ethics application status
Date submitted
25/01/2016
Date registered
17/02/2016
Date last updated
22/12/2023

Titles & IDs
Public title
A Study of Avelumab With Axitinib Versus Sunitinib In Advanced Renal Cell Cancer (JAVELIN Renal 101)
Scientific title
A PHASE 3, MULTINATIONAL, RANDOMIZED, OPEN-LABEL, PARALLEL-ARM STUDY OF AVELUMAB (MSB0010718C) IN COMBINATION WITH AXITINIB (INLYTA(REGISTERED)) VERSUS SUNITINIB (SUTENT(REGISTERED)) MONOTHERAPY IN THE FIRST-LINE TREATMENT OF PATIENTS WITH ADVANCED RENAL CELL CARCINOMA
Secondary ID [1] 0 0
2015-002429-20
Secondary ID [2] 0 0
B9991003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Cell Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Avelumab (MSB0010718C)
Treatment: Drugs - Axitinib (AG-013736)
Treatment: Drugs - Sunitinib

Experimental: Avelumab in combination with axitinib - Avelumab administered at 10 mg/kg IV every two weeks in combination with axitinib, 5 mg PO BID.

Active Comparator: Sunitinib - Sunitinib given at 50 mg PO QD on schedule 4/2


Treatment: Drugs: Avelumab (MSB0010718C)
IV treatment Avelumab administered at 10 mg/kg IV every two weeks

Treatment: Drugs: Axitinib (AG-013736)
Oral treatment Axitinib given 5 mg PO BID

Treatment: Drugs: Sunitinib
Oral treatment Sunitinib given at 50 mg PO QD on schedule 4/2
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) in PD-L1 positive patients
Timepoint [1] 0 0
From randomization up to 40 months.
Primary outcome [2] 0 0
Overall Survival in PD-L1 positive patients
Timepoint [2] 0 0
Every 3 months up to 8 years
Secondary outcome [1] 0 0
Overall Survival (OS) in unselected patients
Timepoint [1] 0 0
Every 3 months up to 8 years
Secondary outcome [2] 0 0
Number of participants with Objective Response (OR)
Timepoint [2] 0 0
Every 6 weeks up to 18 months from patient enrollment in the study, then every 12 weeks up to 40 months from randomization
Secondary outcome [3] 0 0
Disease Control (DC)
Timepoint [3] 0 0
Every 6 weeks up to 18 months from patient enrollment in the study, then every 12 weeks up to 40 months from randomization
Secondary outcome [4] 0 0
Time to Tumor Response (TTR)
Timepoint [4] 0 0
Every 6 weeks up to 18 months from patient enrollment in the study, then every 12 weeks up to 40 months from randomization
Secondary outcome [5] 0 0
Duration of response (DR)
Timepoint [5] 0 0
Every 6 weeks up to 18 months from patient enrollment in the study, then every 12 weeks up to 40 months from randomization
Secondary outcome [6] 0 0
Progression Free Survival (PFS) by Investigator assessment
Timepoint [6] 0 0
Every 6 weeks up to 18 months from patient enrollment in the study, then every 12 weeks up to 40 months from randomization
Secondary outcome [7] 0 0
Trough plasma concentration (Ctrough) of avelumab
Timepoint [7] 0 0
Pre-dose
Secondary outcome [8] 0 0
Trough plasma concentration (Ctrough) of axitinib
Timepoint [8] 0 0
Pre-dose
Secondary outcome [9] 0 0
Maximum plasma concentration (Cmax) of axitinib
Timepoint [9] 0 0
2 hours post-dose
Secondary outcome [10] 0 0
Anti-Drug Antibody (ADA) levels of avelumab/Neutralizing antibodies titers for MSB0010718C
Timepoint [10] 0 0
Pre-dose
Secondary outcome [11] 0 0
Tumor tissue biomarker status
Timepoint [11] 0 0
Baseline
Secondary outcome [12] 0 0
Overall Survival (OS) in biomarker-positive and biomarker-negative subgroups
Timepoint [12] 0 0
Baseline
Secondary outcome [13] 0 0
Change From Baseline in FACT-Kidney Symptom Index (FKSI)-19
Timepoint [13] 0 0
Every 6 weeks up to 8 years
Secondary outcome [14] 0 0
Change from Baseline in European Quality of Life Questionnaire (EQ-5D) - Health State Profile
Timepoint [14] 0 0
Every 6 weeks up to 8 years
Secondary outcome [15] 0 0
Progression Free Survival (PFS) in biomarker-positive and biomarker-negative subgroups
Timepoint [15] 0 0
Baseline
Secondary outcome [16] 0 0
Objective Response (OR) in biomarker-positive and biomarker-negative subgroups
Timepoint [16] 0 0
Baseline
Secondary outcome [17] 0 0
Disease Control (DC) in biomarker-positive and biomarker-negative subgroups
Timepoint [17] 0 0
Baseline
Secondary outcome [18] 0 0
Time To Response (TTR) in biomarker-positive and biomarker-negative subgroups
Timepoint [18] 0 0
Baseline
Secondary outcome [19] 0 0
Duration of Response (DR) in biomarker-positive and biomarker-negative subgroups
Timepoint [19] 0 0
Baseline
Secondary outcome [20] 0 0
Change from Baseline in European Quality of Life Questionnaire (EQ-5D) - Visual Analogic Scale
Timepoint [20] 0 0
Every 6 weeks up to 8 years
Secondary outcome [21] 0 0
Time to treatment discontinuation/failure due to toxicity (TTF)
Timepoint [21] 0 0
From Cycle 1 Day 1, every 6 weeks up to the End of Treatment
Secondary outcome [22] 0 0
Treatment discontinuation/failure due to toxicity
Timepoint [22] 0 0
From Cycle 1 Day 1, every 6 weeks up to the End of Treatment
Secondary outcome [23] 0 0
PFS on next-line therapy (PFS2)
Timepoint [23] 0 0
From randomization up to 8 years.
Secondary outcome [24] 0 0
Progression Free Survival (PFS) in unselected patients
Timepoint [24] 0 0
From randomization up to 40 months.

Eligibility
Key inclusion criteria
- Histologically or cytologically confirmed advanced or metastatic RCC with clear cell
component

- Availability of a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block from a
de novo tumor biopsy during screening (biopsied tumor lesion should not be a RECIST
target lesion). Alternatively, a recently obtained archival FFPE tumor tissue block
(not cut slides) from a primary or metastatic tumor resection or biopsy can be
provided if the following criteria are met: 1) the biopsy or resection was performed
within 1 year of randomization AND 2) the patient has not received any intervening
systemic anti-cancer treatment from the time the tissue was obtained and randomization
onto the current study. If an FFPE tissue block cannot be provided as per documented
regulations then, 15 unstained slides (10 minimum) will be acceptable

- Availability of an archival FFPE tumor tissue from primary tumor resection specimen
(if not provided per above). If an FFPE tissue block cannot be providedas per
documented regulations 15 unstained slides (10 minimum) will be acceptable

- At least one measureable lesion as defined by RECIST version 1.1 that has not been
previously irradiated

- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

- Adequate bone marrow function, renal and liver functions
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior systemic therapy directed at advanced or metastatic RCC

- Prior adjuvant or neoadjuvant therapy for RCC if disease progression or relapse has
occurred during or within 12 months after the last dose of treatment.

- Prior immunotherapy with IL-2, IFN-a, or anti PD 1, anti PD L1, anti PD L2, anti
CD137, or anti cytotoxic T lymphocyte associated antigen 4 (CTLA 4) antibody
(including ipilimumab), or any other antibody or drug specifically targeting T cell co
stimulation or immune checkpoint pathways

- Prior therapy with axitinib and/or sunitinib as well as any prior therapies with other
VEGF pathway inhibitors

- Newly dignosed or active brain metastasis

- Known severe hypersensitivity reactions to monoclonal antibodies (Grade =3), any
history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of partially
controlled asthma Global Initiative for Asthma 2011)

- Any of the following in the previous 12 months: myocardial infarction, severe/unstable
angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure,
LVEF less than LLN, clinically significant pericardial effusion, cerebrovascular
accident, transient ischemic attack

- Any of the following in the previous 6 months: deep vein thrombosis or symptomatic
pulmonary embolism

- Vaccination within 4 weeks of the first dose of avelumab and while on trial is
prohibited except for administration of inactivated vaccines (for example, inactivated
influenza vaccines)

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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/03/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
21/05/2024
Actual
Sample size
Target
Accrual to date
Final
888
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Macquarie University Hospital Pharmacy - Macquarie University
Recruitment hospital [2] 0 0
Macquarie University - Macquarie University
Recruitment hospital [3] 0 0
Nuclear Medicine Department - Randwick
Recruitment hospital [4] 0 0
Pharmacy Department, Clinical Trials - Randwick
Recruitment hospital [5] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [6] 0 0
Spectrum Medical Imaging - Randwick
Recruitment hospital [7] 0 0
Division of Cancer Services - Woolloongabba
Recruitment hospital [8] 0 0
BHS Diagnostic Services - Ballarat
Recruitment hospital [9] 0 0
Lake Imaging - Ballarat
Recruitment hospital [10] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [11] 0 0
Eastern Health - Box Hill
Recruitment hospital [12] 0 0
Monash Health Translational Precinct, Monash Medical Centre - Clayton
Recruitment hospital [13] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [14] 0 0
Monash Cancer Centre - East Bentleigh
Recruitment hospital [15] 0 0
Moorabbin Radiology - East Bentleigh
Recruitment hospital [16] 0 0
Slade Health - Mount Waverley
Recruitment hospital [17] 0 0
Ballarat Day Procedure Centre - Wendouree
Recruitment hospital [18] 0 0
Ballarat Oncology & Haematology Services - Wendouree
Recruitment hospital [19] 0 0
Nova Pharmacy - Wendouree
Recruitment hospital [20] 0 0
SKG Radiology - Murdoch
Recruitment hospital [21] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [22] 0 0
St John of God Murdoch Hospital - Murdoch
Recruitment hospital [23] 0 0
EPIC Pharmacy Murdoch - Perth
Recruitment postcode(s) [1] 0 0
2109 - Macquarie University
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
3350 - Ballarat
Recruitment postcode(s) [5] 0 0
3128 - Box Hill
Recruitment postcode(s) [6] 0 0
3168 - Clayton
Recruitment postcode(s) [7] 0 0
3165 - East Bentleigh
Recruitment postcode(s) [8] 0 0
3149 - Mount Waverley
Recruitment postcode(s) [9] 0 0
3355 - Wendouree
Recruitment postcode(s) [10] 0 0
6050 - Murdoch
Recruitment postcode(s) [11] 0 0
6150 - Murdoch
Recruitment postcode(s) [12] 0 0
6150 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Maine
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
Montana
Country [14] 0 0
United States of America
State/province [14] 0 0
Nevada
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Washington
Country [22] 0 0
Austria
State/province [22] 0 0
Wien
Country [23] 0 0
Belgium
State/province [23] 0 0
Brussels
Country [24] 0 0
Belgium
State/province [24] 0 0
Bruxelles
Country [25] 0 0
Belgium
State/province [25] 0 0
Gent
Country [26] 0 0
Belgium
State/province [26] 0 0
Kortrijk
Country [27] 0 0
Belgium
State/province [27] 0 0
Liège
Country [28] 0 0
Canada
State/province [28] 0 0
Alberta
Country [29] 0 0
Canada
State/province [29] 0 0
British Columbia
Country [30] 0 0
Canada
State/province [30] 0 0
Ontario
Country [31] 0 0
Canada
State/province [31] 0 0
Quebec
Country [32] 0 0
Denmark
State/province [32] 0 0
Herlev
Country [33] 0 0
Denmark
State/province [33] 0 0
Odense C
Country [34] 0 0
France
State/province [34] 0 0
Cedex
Country [35] 0 0
France
State/province [35] 0 0
CAEN cedex 05
Country [36] 0 0
France
State/province [36] 0 0
Caen, Cedex 05
Country [37] 0 0
France
State/province [37] 0 0
Le Mans
Country [38] 0 0
France
State/province [38] 0 0
Lyon cedex 8
Country [39] 0 0
France
State/province [39] 0 0
LYON cedex 8
Country [40] 0 0
France
State/province [40] 0 0
Marseille
Country [41] 0 0
France
State/province [41] 0 0
Rennes cedex
Country [42] 0 0
France
State/province [42] 0 0
Saint-Herblain Cedex
Country [43] 0 0
France
State/province [43] 0 0
Vandoeuvre les Nancy
Country [44] 0 0
France
State/province [44] 0 0
Villejuif
Country [45] 0 0
Germany
State/province [45] 0 0
Baden-wuerttemberg
Country [46] 0 0
Germany
State/province [46] 0 0
Thuringia
Country [47] 0 0
Hungary
State/province [47] 0 0
Budapest
Country [48] 0 0
Israel
State/province [48] 0 0
Ramat - GAN
Country [49] 0 0
Israel
State/province [49] 0 0
Beer Yaakov
Country [50] 0 0
Israel
State/province [50] 0 0
Haifa
Country [51] 0 0
Israel
State/province [51] 0 0
Kfar Saba
Country [52] 0 0
Israel
State/province [52] 0 0
Petach Tikva
Country [53] 0 0
Israel
State/province [53] 0 0
Ramat - Gan
Country [54] 0 0
Israel
State/province [54] 0 0
Tel Aviv
Country [55] 0 0
Italy
State/province [55] 0 0
(pn)
Country [56] 0 0
Italy
State/province [56] 0 0
Milan
Country [57] 0 0
Italy
State/province [57] 0 0
Rome
Country [58] 0 0
Japan
State/province [58] 0 0
Aichi
Country [59] 0 0
Japan
State/province [59] 0 0
Aomori
Country [60] 0 0
Japan
State/province [60] 0 0
Hokkaidô
Country [61] 0 0
Japan
State/province [61] 0 0
Iwate
Country [62] 0 0
Japan
State/province [62] 0 0
Kanagawa
Country [63] 0 0
Japan
State/province [63] 0 0
Osaka
Country [64] 0 0
Japan
State/province [64] 0 0
Shizuoka
Country [65] 0 0
Japan
State/province [65] 0 0
Tokyo
Country [66] 0 0
Japan
State/province [66] 0 0
Akita
Country [67] 0 0
Japan
State/province [67] 0 0
Chiba
Country [68] 0 0
Japan
State/province [68] 0 0
Fukuoka
Country [69] 0 0
Japan
State/province [69] 0 0
Niigata
Country [70] 0 0
Japan
State/province [70] 0 0
Tokushima
Country [71] 0 0
Japan
State/province [71] 0 0
Yamagata
Country [72] 0 0
Korea, Republic of
State/province [72] 0 0
Gyeonggi-do
Country [73] 0 0
Korea, Republic of
State/province [73] 0 0
Gyeonggido
Country [74] 0 0
Korea, Republic of
State/province [74] 0 0
Daegu
Country [75] 0 0
Korea, Republic of
State/province [75] 0 0
Daejeon
Country [76] 0 0
Korea, Republic of
State/province [76] 0 0
Seoul
Country [77] 0 0
Mexico
State/province [77] 0 0
Ciudad DE Mexico
Country [78] 0 0
Mexico
State/province [78] 0 0
Nuevo LEON
Country [79] 0 0
Mexico
State/province [79] 0 0
Oaxaca
Country [80] 0 0
Netherlands
State/province [80] 0 0
Noord-holland
Country [81] 0 0
Netherlands
State/province [81] 0 0
Zuid-holland
Country [82] 0 0
Netherlands
State/province [82] 0 0
Eindhoven
Country [83] 0 0
Netherlands
State/province [83] 0 0
Haarlem
Country [84] 0 0
Netherlands
State/province [84] 0 0
Hoofddorp
Country [85] 0 0
Netherlands
State/province [85] 0 0
Maastricht
Country [86] 0 0
Netherlands
State/province [86] 0 0
Veldhoven
Country [87] 0 0
New Zealand
State/province [87] 0 0
Auckland
Country [88] 0 0
New Zealand
State/province [88] 0 0
BAY OF Plenty
Country [89] 0 0
New Zealand
State/province [89] 0 0
Manawatu- Whanganui
Country [90] 0 0
New Zealand
State/province [90] 0 0
Manawatu-wanganui
Country [91] 0 0
New Zealand
State/province [91] 0 0
Tauranga
Country [92] 0 0
New Zealand
State/province [92] 0 0
Wairarapa
Country [93] 0 0
New Zealand
State/province [93] 0 0
Christchurch
Country [94] 0 0
New Zealand
State/province [94] 0 0
Hamilton
Country [95] 0 0
New Zealand
State/province [95] 0 0
Palmerston North
Country [96] 0 0
Romania
State/province [96] 0 0
Cluj-Napoca
Country [97] 0 0
Romania
State/province [97] 0 0
Craiova
Country [98] 0 0
Romania
State/province [98] 0 0
Timisoara
Country [99] 0 0
Russian Federation
State/province [99] 0 0
Kursk Region
Country [100] 0 0
Russian Federation
State/province [100] 0 0
Pesochny
Country [101] 0 0
Russian Federation
State/province [101] 0 0
Poselok Pesochniy
Country [102] 0 0
Russian Federation
State/province [102] 0 0
Saint-petersburg
Country [103] 0 0
Russian Federation
State/province [103] 0 0
Moscow
Country [104] 0 0
Russian Federation
State/province [104] 0 0
Nizhniy Novgorod
Country [105] 0 0
Russian Federation
State/province [105] 0 0
Saint Petersburg
Country [106] 0 0
Russian Federation
State/province [106] 0 0
Yaroslavl
Country [107] 0 0
Spain
State/province [107] 0 0
Navarra
Country [108] 0 0
Spain
State/province [108] 0 0
Madrid
Country [109] 0 0
Spain
State/province [109] 0 0
Sevilla
Country [110] 0 0
Sweden
State/province [110] 0 0
Gothenburg
Country [111] 0 0
United Kingdom
State/province [111] 0 0
Cambridgeshire
Country [112] 0 0
United Kingdom
State/province [112] 0 0
Middlesex
Country [113] 0 0
United Kingdom
State/province [113] 0 0
Surrey, London
Country [114] 0 0
United Kingdom
State/province [114] 0 0
Surrey
Country [115] 0 0
United Kingdom
State/province [115] 0 0
Cambridge
Country [116] 0 0
United Kingdom
State/province [116] 0 0
Glasgow
Country [117] 0 0
United Kingdom
State/province [117] 0 0
London
Country [118] 0 0
United Kingdom
State/province [118] 0 0
Manchester
Country [119] 0 0
United Kingdom
State/province [119] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a phase 3 randomized trial evaluating the anti-tumor activity and safety of avelumab
in combination with axitinib and of sunitinib monotherapy, administered as first-line
treatment, in patients with advanced renal cell carcinoma
Trial website
https://clinicaltrials.gov/ct2/show/NCT02684006
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
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