Clinical Trials /

Study of PF-06801591 in Combination With Bacillus Calmette-Guerin (BCG) in Participants With High-Risk Non-Muscle Invasive Bladder Cancer.

NCT04165317

Description:

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

Related Conditions:
  • Bladder Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of 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
  • NCT ID: NCT04165317

Conditions

  • Non-muscle Invasive Bladder Cancer

Interventions

DrugSynonymsArms
PF-06801591PF-06801591 + BCG induction and maintenance
Bacillus Calmette-GuerinBCGBacillus Calmette Guerin

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
PF-06801591 + BCG induction and maintenanceExperimentalPF-06801591 in combination with Bacillus Calmette Guerin(induction+maintenance).
  • PF-06801591
  • Bacillus Calmette-Guerin
PF-06801591 + BCG induction onlyExperimentalPF-06801591 in combination with Bacillus Calmette Guerin (induction only).
  • PF-06801591
  • Bacillus Calmette-Guerin
Bacillus Calmette GuerinActive ComparatorBacillus Calmette Guerin (induction and maintenance).
  • Bacillus Calmette-Guerin

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 9(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

  • PF-06801591
  • Bacillus Calmette Guerin
  • BCG
  • Bladder cancer

Last Updated

January 15, 2020