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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04165317
Ethics application status
Date submitted
13/11/2019
Date registered
15/11/2019
Date last updated
25/11/2024

Titles & IDs
Public title
A Study of Sasanlimab in People With 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 or PF-06801591 as a Single Agent in Participants With BCG-Unresponsive NMIBC
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
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders

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).

Experimental: BCG Unresponsive CIS - PF-06801591

Experimental: BCG Unresponsive NMIBC - PF-06801591


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 (Cohort A: Arm A compared to Arm C)
Timepoint [1] 0 0
55 months after first participant randomized
Primary outcome [2] 0 0
Complete response rate (Cohort B1) (Obsolete after stopping enrollment in Cohort B)
Timepoint [2] 0 0
Registration to 12 months after last participant initially assessed
Primary outcome [3] 0 0
Event free survival (Cohort B2) (Obsolete after stopping enrollment in Cohort B)
Timepoint [3] 0 0
Registration to 12 months after last participant initially assessed
Secondary outcome [1] 0 0
Event free survival (Cohort A: Arm B compared to Arm C)
Timepoint [1] 0 0
55 months after first participant randomized
Secondary outcome [2] 0 0
Overall Survival (Cohort A: Arm A compared to Arm C)
Timepoint [2] 0 0
Randomization up to 60 months from last participant randomized
Secondary outcome [3] 0 0
Overall Survival (Cohort A: Arm B compared to Arm C)
Timepoint [3] 0 0
Randomization up to 60 months from last participant randomized
Secondary outcome [4] 0 0
Complete response rate in participants with CIS at randomization (Cohort A: Arm A, B, C)
Timepoint [4] 0 0
Randomization up to 60 months from last participant randomized
Secondary outcome [5] 0 0
Disease-specific survival (Cohort A: Arm A, B, C)
Timepoint [5] 0 0
Randomization up to 60 months from last participant randomized
Secondary outcome [6] 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) (Obsolete for Cohort B after stopping enrollment)
Timepoint [6] 0 0
Randomization up to 60 months from last participant randomized
Secondary outcome [7] 0 0
ctrough of PF-06801591 when in combination with BCG (induction and maintenance or induction). Cohort A: Arms A and B only.
Timepoint [7] 0 0
Randomization up to 24 months
Secondary outcome [8] 0 0
Incidence of ADA/Nab of PF-06801591 when in combination with BCG (induction and maintenance or induction). Cohort A: Arms A and B only.
Timepoint [8] 0 0
Randomization up to 24 months
Secondary outcome [9] 0 0
Tumor sample biomarker status based on PD-L1 expression (high or low) (Obsolete for Cohort B after stopping enrollment)
Timepoint [9] 0 0
Baseline
Secondary outcome [10] 0 0
Duration of CR for participants with CIS at randomization (Obsolete for Cohort B after stopping enrollment)
Timepoint [10] 0 0
Randomization/registration up to 60 months from last participant randomized
Secondary outcome [11] 0 0
Time to recurrence of low grade disease (Cohort A: Arm A, B, C)
Timepoint [11] 0 0
Randomization up to 60 months from last participant randomized
Secondary outcome [12] 0 0
Time to cystectomy (Obsolete for Cohort B after stopping enrollment)
Timepoint [12] 0 0
Randomization/registration to date of cystectomy (up to 5 years after last participant is randomized)
Secondary outcome [13] 0 0
Health-related quality of life as measured by PTAB (Patient Treatment Administration Burden Questionnaire) (Obsolete for Cohort B after stopping enrollment)
Timepoint [13] 0 0
Randomization/registration up to 24 months
Secondary outcome [14] 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 (Obsolete for Cohort B after stopping enrollment)
Timepoint [14] 0 0
Baseline up to 60 months from the last participant randomized
Secondary outcome [15] 0 0
Percentage of Participants With Laboratory Abnormalities (Obsolete for Cohort B after stopping enrollment)
Timepoint [15] 0 0
Baseline up to 60 months from last participant randomized
Secondary outcome [16] 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) (Obsolete for Cohort B after stopping enrollment)
Timepoint [16] 0 0
Randomization/registration up to 60 months from the last participant randomized
Secondary outcome [17] 0 0
Complete response rate at 12 months (Cohort B1) (Obsolete after stopping enrollment in Cohort B)
Timepoint [17] 0 0
12 months after last participant's initial assessment
Secondary outcome [18] 0 0
Event Free Survival (Cohort B1) (Obsolete after stopping enrollment in Cohort B)
Timepoint [18] 0 0
Registration to 5 years after last participant randomized.
Secondary outcome [19] 0 0
Overall Survival (Cohorts B1 and B2) (Obsolete after stopping enrollment in Cohort B)
Timepoint [19] 0 0
Registration to 5 years after last participant randomized.
Secondary outcome [20] 0 0
ctrough of PF-06801591 (Cohorts B1 and B2) (Obsolete after stopping enrollment in Cohort B)
Timepoint [20] 0 0
Registration up to 24 months
Secondary outcome [21] 0 0
Incidence of ADA/Nab of PF-06801591 (Cohorts B1 and B2) (Obsolete after stopping enrollment in Cohort B)
Timepoint [21] 0 0
Registration up to 24 months
Secondary outcome [22] 0 0
cmax of PF-06801591 (Cohort B2 only) (Obsolete after stopping enrollment in Cohort B)
Timepoint [22] 0 0
Registration up to 24 months

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 positive TURBT occurring within 12 weeks prior to randomization or study intervention. A second TURBT must have been performed if indicated according to the current locally applicable guidelines, ie, American Urological Association, European Association of Urology
* (Cohorts B1 and B2 only): Histological confirmed diagnosis of BCG-unresponsive high-risk, non-muscle invasive TCC of the urothelium within 12 months (CIS only) or 6 months (recurrent Ta/T1 disease) of completion of adequate BCG therapy.
* Have refused or are ineligible for radical cystectomy
Minimum age
18 Years
Maximum age
No limit
Sex
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
* (Cohort A only): Intravesical BCG therapy within 2 years prior to randomization. Prior intravesical chemotherapy for NMIBC is allowed.

(Cohorts B1 and B2 only): Any systemic or intravesical chemotherapy or immunotherapy from the time of most recent positive TURBT to initiation of study intervention.

* 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
* (Cohorts B1 and B2 only): Prior participation in Cohort A of this study.

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
30/12/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
2/12/2026
Actual
Sample size
Target
Accrual to date
Final
1070
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Southern Highlands Cancer Centre - Bowral
Recruitment hospital [2] 0 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [3] 0 0
Campbelltown Private Hospital - Campbelltown
Recruitment hospital [4] 0 0
Chris O'Brien Lifehouse Hospital - Camperdown
Recruitment hospital [5] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [6] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [7] 0 0
Eastern Clinical Research Unit - Box Hill
Recruitment hospital [8] 0 0
Yarra Ranges Health - Lilydale
Recruitment postcode(s) [1] 0 0
2756 - Bowral
Recruitment postcode(s) [2] 0 0
2560 - Campbelltown
Recruitment postcode(s) [3] 0 0
2050 - Camperdown
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
3140 - Lilydale
Recruitment outside Australia
Country [1] 0 0
United States of America
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Arizona
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United States of America
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Arkansas
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California
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United States of America
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Colorado
Country [5] 0 0
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Florida
Country [6] 0 0
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Illinois
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Louisiana
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Maryland
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United States of America
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Michigan
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New York
Country [11] 0 0
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Oregon
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South Carolina
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United States of America
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Texas
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United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
Belgium
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Gent
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Canada
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British Columbia
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Canada
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Ontario
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Canada
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Quebec
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China
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Anhui
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China
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Beijing
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China
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Fujian
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China
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Hubei
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China
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Hunan
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China
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China
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Zhejiang
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China
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China
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Shanghai
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China
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Tianjin
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Antony
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Bayonne
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Brest
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Nuertingen
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Tuebingen
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Catania
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Kaluzhskaya OBL.
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Russian Federation
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Republic OF Mordovia
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Nizhny Novgorod
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Omsk
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Ryazan
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Saint Petersburg
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Ufa
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Vologda
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Yaroslavl
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Spain
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Barcelona
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Madrid
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Navarra
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Tarragona
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A Coruna
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Spain
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Caceres
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Girona
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Llíria
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Lugo
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Spain
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Valencia
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United Kingdom
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London

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

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to learn about the safety and effects of the study medicine (sasanlimab) in people with non-muscle invasive bladder cancer. This study is seeking participants whose bladder cancer is still in early stages, has not spread outside of the bladder, has been removed with surgery, and is high risk (Part A) or was previously treated with BCG (Bacillus Calmette Guerin), a standard treatment for bladder cancer (Part B).

In Part A (enrollment closed), each participant was assigned to one of three study treatment groups.

* One group is given sasanlimab and BCG at the study clinic.
* The second group is given sasanlimab and BCG at the study clinic. This group will receive BCG for the first six weeks only.
* The third group is given BCG only and will not receive sasanlimab.

In Part B of the study, each new participant will be assigned to a study treatment group based on the type of their bladder tumor.

- Both groups will be given sasanlimab at the study clinic.

On August 31, 2022, the Sponsor announced the discontinuation of enrollment to Part B. The decision to discontinue enrollment to Part B was not made for safety reasons.
Trial website
https://clinicaltrials.gov/study/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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

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