Description:
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.
Title
- Brief Title: Study of Sasanlimab (PF-06801591) in Combination With Bacillus Calmette-Guerin (BCG) in Participants With High-Risk Non-Muscle Invasive Bladder Cancer
- Official 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
Clinical Trial IDs
- ORG STUDY ID:
B8011006
- SECONDARY ID:
2019-003375-19
- NCT ID:
NCT04165317
Conditions
- Non-muscle Invasive Bladder Cancer
Interventions
Drug | Synonyms | Arms |
---|
PF-06801591 | Sasanlimab | PF-06801591 + BCG induction and maintenance |
Bacillus Calmette-Guerin | BCG | BCG induction and maintenance |
Purpose
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 Arms
Name | Type | Description | Interventions |
---|
PF-06801591 + BCG induction and maintenance | Experimental | PF-06801591 in combination with Bacillus Calmette Guerin(induction+maintenance). | - PF-06801591
- Bacillus Calmette-Guerin
|
PF-06801591 + BCG induction only | Experimental | PF-06801591 in combination with Bacillus Calmette Guerin (induction only). | - PF-06801591
- Bacillus Calmette-Guerin
|
BCG induction and maintenance | Active Comparator | Bacillus Calmette Guerin (induction and maintenance). | |
Eligibility Criteria
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
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Event free survival (Arm A compared to Arm C) |
Time Frame: | Randomization up to 55 months |
Safety Issue: | |
Description: | Event free survival is defined as the time from randomization to date of EFS event. |
Secondary Outcome Measures
Measure: | Overall Survival (Arm A compared to Arm C) |
Time Frame: | Randomization up to 60 months from last participant randomized |
Safety Issue: | |
Description: | Overall survival is defined as the time from the date of randomization to the date of death due to any cause. |
Measure: | Overall Survival (Arm B compared to Arm C) |
Time Frame: | Randomization up to 60 months from last participant randomized |
Safety Issue: | |
Description: | Overall survival is defined as the time from the date of randomization to the date of death due to any cause. |
Measure: | Complete response in participants with CIS at randomization |
Time Frame: | Randomization up to 60 months from last participant randomized |
Safety Issue: | |
Description: | Number of CIS participants with complete response. |
Measure: | Disease-specific survival |
Time Frame: | Randomization up to 60 months from last participant randomized |
Safety Issue: | |
Description: | Disease specific survival (DSS) is defined as the time from randomization to death resulting from bladder cancer. |
Measure: | Health-related quality of life as measured by EORTC QLQ-C30 (European Organization for Treatment of Cancer Quality of Life Questionnaire for cancer patients) |
Time Frame: | Randomization up to 60 months from last participant randomized |
Safety Issue: | |
Description: | 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). |
Measure: | ctrough of PF-06801591 when in combination with BCG (induction and maintenance or induction). Arms A and B only. |
Time Frame: | Randomization up to 24 months |
Safety Issue: | |
Description: | Ctrough will be summarized in Arms A and B only. |
Measure: | Incidence of ADA/Nab of PF-06801591 when in combination with BCG (induction and maintenance or induction). Arms A and B only. |
Time Frame: | Randomization up to 24 months |
Safety Issue: | |
Description: | Immunogenicity will be evaluated for Arms A and B only. |
Measure: | Tumor sample biomarker status based on PD-L1 expression (high or low) |
Time Frame: | Baseline |
Safety Issue: | |
Description: | Evaluate PD-L1 expression. |
Measure: | Duration of CR for participants with CIS at randomization |
Time Frame: | Randomization up to 60 months from last participant randomized |
Safety Issue: | |
Description: | Duration of CR is defined as time from first CR to first recurrence or death due to any cause, whichever occurs first. |
Measure: | Time to recurrence of low grade disease |
Time Frame: | Randomization up to 60 months from last participant randomized |
Safety Issue: | |
Description: | 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. |
Measure: | Time to cystectomy |
Time Frame: | Randomization to date of cystectomy (up to 5 years after last participant is randomized) |
Safety Issue: | |
Description: | Time to cystectomy is defined as time from randomization to cystectomy in participants with NMIBC |
Measure: | Health-related quality of life as measured by PTAB (Patient Treatment Administration Burden Questionnaire) |
Time Frame: | Randomization up to 24 months |
Safety Issue: | |
Description: | 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). |
Measure: | Percentage of Participants With All Causality and Treatment-related Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Withdrawals Due to TEAEs |
Time Frame: | Baseline up to 60 months from the last participant randomized |
Safety Issue: | |
Description: | 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. |
Measure: | Percentage of Participants With Laboratory Abnormalities |
Time Frame: | Baseline up to 60 months from last participant randomized |
Safety Issue: | |
Description: | 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. |
Measure: | 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) |
Time Frame: | Randomization up to 60 months from the last participant randomized |
Safety Issue: | |
Description: | 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). |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Pfizer |
Trial Keywords
- CREST
- Sasanlimab
- PF-06801591
- Bacillus Calmette Guerin
- BCG
- Bladder cancer
Last Updated
August 18, 2021