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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04165317




Registration number
NCT04165317
Ethics application status
Date submitted
13/11/2019
Date registered
15/11/2019
Date last updated
22/04/2021

Titles & IDs
Public title
Study of Sasanlimab (PF-06801591) in Combination With Bacillus Calmette-Guerin (BCG) in Participants With High-Risk Non-Muscle Invasive Bladder Cancer
Scientific title
A Phase 3, Multinational, Randomized, Open-Label, Three Parallel-Arm Study of PF-06801591, an Anti-PD-1 Antibody, in Combination With Bacillus Calmette-Guerin (BCG Induction With or Without BCG Maintenance) Versus BCG (Induction and Maintenance) in Participants With High-Risk, BCG-Naïve Non-Muscle Invasive Bladder Cancer
Secondary ID [1] 0 0
2019-003375-19
Secondary ID [2] 0 0
B8011006
Universal Trial Number (UTN)
Trial acronym
CREST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-muscle Invasive Bladder Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bladder - transitional cell cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PF-06801591
Treatment: Drugs - Bacillus Calmette-Guerin

Experimental: PF-06801591 + BCG induction and maintenance - PF-06801591 in combination with Bacillus Calmette Guerin(induction+maintenance).

Experimental: PF-06801591 + BCG induction only - PF-06801591 in combination with Bacillus Calmette Guerin (induction only).

Active Comparator: BCG induction and maintenance - Bacillus Calmette Guerin (induction and maintenance).


Treatment: Drugs: PF-06801591
A monoclonal antibody (mAb) that blocks the interaction between PD-1 and PD-L1/PD-L2.

Treatment: Drugs: Bacillus Calmette-Guerin
Immunotherapy treatment approved by FDA for patients with high-risk non-muscle invasive bladder cancer

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event free survival (Arm A compared to Arm C) - Event free survival is defined as the time from randomization to date of EFS event.
Timepoint [1] 0 0
Randomization up to 55 months
Primary outcome [2] 0 0
Event free survival (Arm B compared to Arm C) - Event free survival is defined as the time from randomization to date of EFS event.
Timepoint [2] 0 0
Randomization up to 55 months
Secondary outcome [1] 0 0
Overall Survival (Arm A compared to Arm C) - Overall survival is defined as the time from the date of randomization to the date of death due to any cause.
Timepoint [1] 0 0
Randomization up to 60 months from last participant randomized
Secondary outcome [2] 0 0
Overall Survival (Arm B compared to Arm C) - Overall survival is defined as the time from the date of randomization to the date of death due to any cause.
Timepoint [2] 0 0
Randomization up to 60 months from last participant randomized
Secondary outcome [3] 0 0
Complete response in participants with CIS at randomization - Number of CIS participants with complete response.
Timepoint [3] 0 0
Randomization up to 60 months from last participant randomized
Secondary outcome [4] 0 0
Disease-specific survival - Disease specific survival (DSS) is defined as the time from randomization to death resulting from bladder cancer.
Timepoint [4] 0 0
Randomization up to 60 months from last participant randomized
Secondary outcome [5] 0 0
Health-related quality of life as measured by EORTC QLQ-C30 (European Organization for Treatment of Cancer Quality of Life Questionnaire for cancer patients) - EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties).
Timepoint [5] 0 0
Randomization up to 60 months from last participant randomized
Secondary outcome [6] 0 0
ctrough of PF-06801591 when in combination with BCG (induction and maintenance or induction). Arms A and B only. - Ctrough will be summarized in Arms A and B only.
Timepoint [6] 0 0
Randomization up to 24 months
Secondary outcome [7] 0 0
Incidence of ADA/Nab of PF-06801591 when in combination with BCG (induction and maintenance or induction). Arms A and B only. - Immunogenicity will be evaluated for Arms A and B only.
Timepoint [7] 0 0
Randomization up to 24 months
Secondary outcome [8] 0 0
Tumor sample biomarker status based on PD-L1 expression (high or low) - Evaluate PD-L1 expression.
Timepoint [8] 0 0
Baseline
Secondary outcome [9] 0 0
Duration of CR for participants with CIS at randomization - Duration of CR is defined as time from first CR to first recurrence or death due to any cause, whichever occurs first.
Timepoint [9] 0 0
Randomization up to 60 months from last participant randomized
Secondary outcome [10] 0 0
Time to recurrence of low grade disease - Time to recurrence defined as time from randomization to the date of first documentation of recurrence of low grade disease or death due to any cause, whichever occurs first.
Timepoint [10] 0 0
Randomization up to 60 months from last participant randomized
Secondary outcome [11] 0 0
Time to cystectomy - Time to cystectomy is defined as time from randomization to cystectomy in participants with NMIBC
Timepoint [11] 0 0
Randomization to date of cystectomy (up to 5 years after last participant is randomized)
Secondary outcome [12] 0 0
Health-related quality of life as measured by PTAB (Patient Treatment Administration Burden Questionnaire) - PTAB is a 2-item PRO designed to assess, from the patient perspective, any pain associated with the treatment administration and the burden of the amount of time required to complete the treatment administration procedures (1 item each).
Timepoint [12] 0 0
Randomization up to 24 months
Secondary outcome [13] 0 0
Percentage of Participants With All Causality and Treatment-related Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Withdrawals Due to TEAEs - An adverse event (AE) is any untoward medical occurrence attributed to study drug in a participant who received study drug. AEs comprised both SAEs and non-SAEs. Causality assessment is made by the investigator. Grading is per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) version 3.0.
Timepoint [13] 0 0
Baseline up to 60 months from the last participant randomized
Secondary outcome [14] 0 0
Percentage of Participants With Laboratory Abnormalities - Percentage of participants with laboratory test abnormalities without regard to baseline abnormality. Grading is per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) version 3.0.
Timepoint [14] 0 0
Baseline up to 60 months from last participant randomized
Secondary outcome [15] 0 0
Health-related quality of life as measured by EORTC QLQ-NMIBC24 (European Organization for Treatment of Cancer in patients with non-muscle invasion bladder cancer) - EORTC-QLQ-NMIBC24 has 24 items which can be grouped into 6 subscales: urinary symptoms (7 items), malaise (2 items), future worries (4 items), bloating/flatulence (2 items), sexual functioning (2 items), and male sexual issues (2 items). The NMIBC24 also assesses intravesical treatment, female sexual issues, sexual intimacy, risk of contaminating a partner, and sexual enjoyment (1 item each).
Timepoint [15] 0 0
Randomization up to 60 months from the last participant randomized

Eligibility
Key inclusion criteria
- Histological confirmed diagnosis of high risk non-muscle invasive transitional cell
carcinoma (TCC) of the urothelium of the urinary bladder (tumors of mixed
transitional/non-transitional cell histology are allowed, but TCC must be the
predominant histology)

- Complete resection of all Ta/T1 papillary disease (including participants with
concurrent CIS), with most recent TURBT occurring within 12 weeks prior to
randomization. A second TURBT must have been performed if indicated according to the
current locally applicable guidelines, ie, American Urological Association, European
Association of Urology
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Evidence of muscle-invasive, locally advanced or metastatic urothelial cancer or
concurrent extravesical, non-muscle invasive TCC of the urothelium

- Intravesical BCG therapy within 2 years prior to randomization. Prior intravesical
chemotherapy for NMIBC is allowed

- Prior immunotherapy with anti PD-1, anti PD-L1, anti PD-L2, or anti cytotoxic
T-lymphocyte-associated antigen-4 (CTLA-4) antibody

- Prior treatment with immunostimulatory agents including interleukin (IL)-2, IL-15,
interferon (INF)

- Prior radiation therapy to the bladder

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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Southern Highlands Cancer Centre - Bowral
Recruitment hospital [2] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [3] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [4] 0 0
Eastern Clinical Research Unit - Box Hill
Recruitment hospital [5] 0 0
Monash Health - Clayton
Recruitment hospital [6] 0 0
Yarra Ranges Health - Lilydale
Recruitment postcode(s) [1] 0 0
2756 - Bowral
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
3128 - Box Hill
Recruitment postcode(s) [4] 0 0
3168 - Clayton
Recruitment postcode(s) [5] 0 0
3140 - Lilydale
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
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
Illinois
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
Maryland
Country [9] 0 0
United States of America
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Michigan
Country [10] 0 0
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Minnesota
Country [11] 0 0
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Missouri
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New York
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Ohio
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South Carolina
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Virginia
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Belgium
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Gent
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State/province [18] 0 0
Ontario
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State/province [19] 0 0
Quebec
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China
State/province [20] 0 0
Beijing
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China
State/province [21] 0 0
Fujian
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China
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Hubei
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China
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Jiangsu
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China
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Zhejiang
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China
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Chongqing
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China
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Shanghai
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Antony
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Bayonne
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France
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BORDEAUX Cedex
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France
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Bordeaux
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Brest
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Lille
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Limoges
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Muenster
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Nuertingen
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Tuebingen
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Catania
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Ivanovo
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Kaluga
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Moscow
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Nizhny Novgorod
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Omsk
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Ufa
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Vologda
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
CREST: Combination of sasanlimab and alternative BCG Regimens to Evaluate outcomes with
Subcutaneous anti-PD-1 Treatment

Phase 3 Design with 3 study Arms (A, B and C). Arms A and B consists of two study drugs,
PF-06801591 plus BCG. Arm C consists of one study drug, BCG.

The study is designed to demonstrate that PF-06801591 plus Bacillus Calmette Guerin (BCG)
(induction and maintenance periods) is superior to BCG alone (induction and maintenance
periods) in prolonging event free survival (EFS) in participants with high-risk naïve
non-muscle invasive bladder cancer (NMIBC) and to demonstrate that PF-06801591 plus BCG
(induction period only) is superior to BCG alone (induction and maintenance periods) in
prolonging EFS in participants with high-risk NMIBC.
Trial website
https://clinicaltrials.gov/show/NCT04165317
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
Pfizer CT.gov Call Center
Address 0 0
Country 0 0
Phone 0 0
1-800-718-1021
Fax 0 0
Email 0 0
ClinicalTrials.gov_Inquiries@pfizer.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04165317