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BCG in Combination With Durvalumab in Adult BCG-naïve, High-risk NMIBC Participants (PATAPSCO)

Primary Purpose

Non-Muscle- Invasive Bladder Cancer

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Durvalumab
BCG
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Muscle- Invasive Bladder Cancer focused on measuring Bacillus Calmette-Guerin (BCG), BCG-naïve, immunotherapeutics, human mAb, Durvalumab, non-muscle-invasive bladder cancer (NMIBC)

Eligibility Criteria

18 Years - 130 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: BCG-naïve (defined as participants not having received prior intravesical BCG or who previously received but stopped BCG more than 3 years before study entry). Local histological confirmation (based on cytology and/or pathology report) of high-risk transitional cell carcinoma of the urothelium of the urinary bladder confined to the mucosa or submucosa. Complete resection of all Ta/T1 papillary disease prior to enrollment, with the transurethral resection of bladder tumor (TURBT) removing high-risk NMIBC (non-muscle invasive bladder cancer) performed not more than 4 months before enrollment in the study. No prior radiotherapy for bladder cancer. A life expectancy of at least 12 weeks (90 days). Adequate organ and marrow function World Health Organization/Eastern Cooperative Oncology Group performance status of 0 or 1 at screening No prior exposure to immune-mediated therapy of cancer A candidate for BCG treatment. Local histological confirmation (based on cytology and/or pathology report) of high-risk transitional cell carcinoma of the urothelium of the urinary bladder confined to the mucosa or submucosa. A high-risk tumor is defined as one of the following: T1 tumor; High-grade/G3 tumor; CIS. Exclusion Criteria: Evidence of muscle-invasive, locally advanced, metastatic, and/or extra-vesical bladder cancer (ie, T2, T3, T4, and / or Stage IV). Predominantly variant histology such as micropapillary, plasmacytoid, nested, sarcomatoid, microcystic, squamous and adeno variants of UC representing > 50% of tumor tissue or other than urothelial tumors as assessed by pathology. Evidence of lymphovascular invasion of bladder tumor, except if treatment with BCG is deemed to be the only clinically viable treatment. Immediate cystectomy is indicated. Known or documented absolute and/or relative contraindication of adjuvant intravesical BCG treatment. Concurrent extravesical, non-muscle-invasive transitional cell carcinoma of the urothelium. History of allogenic organ transplantation. Participants with any history of allogenic stem cell transplantation are also excluded. Active or prior documented autoimmune or inflammatory disorders. Participants with hypothyroidism stable on hormone replacement. History of active primary immunodeficiency. Active infection including hepatitis B (known positive HBV/HBsAg result), HCV, or HIV 1/2 (positive HIV) antibodies. Current or prior use of immunosuppressive medication within 14 days before the first durvalumab dose. Female participants who are pregnant or breastfeeding or male or female participants of reproductive potential who are not willing to employ highly effective birth control. Any concurrent chemotherapy, study intervention, biologic or hormonal therapy for cancer treatment; uncontrolled intercurrent illness; History of another primary malignancy except for Malignancy treated with curative intent and with no known active disease ≥ 2 years; Adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease; Adequately treated CIS without evidence of disease; Prostate cancer of stage ≤ T2cN0M0 without biochemical recurrence or progression that in the opinion of the Investigator does not require active intervention. Previous or concurrent treatment with potent systemic immunostimulatory agents

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research SiteRecruiting
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Durvalumab + BCG

Arm Description

Participants will receive Durvalumab for 13 cycles every 4 weeks (q4w) for a maximum 12 months. All participants will receive BCG (supplied by the site) intravesically, as induction weekly for 6 weeks. Patients will subsequently receive BCG for maintenance for 3 weekly doses at 3,6,12,18, and up to 24 months, at the physician's discretion.

Outcomes

Primary Outcome Measures

Incidence of Grade 3 or 4 Possibly related adverse events (PRAEs)
A PRAE is defined as an AE that has been assessed by the Investigator to be possibly related to study treatment. A PRAE will be included if it has onset or worsens (by Investigator report of an increase in CTCAE (common terminology criteria for adverse events) grade relative to pre-treatment) within 6 months of initiation of study intervention and it has CTCAE Grade 3 or 4 recorded within this timeframe.

Secondary Outcome Measures

Number of participants with adverse events (AEs)
To further assess the safety and tolerability of durvalumab + BCG (induction and maintenance) combination therapy in high risk NMIBC participants. Number of participants with adverse events (AEs), including PRAEs, adverse events of special interest (AESIs), immune-mediated AEs, serious adverse events (SAEs), AEs resulting in treatment interruption and discontinuation will be assessed.
Percentage of patient-reported treatment tolerability symptoms assessed using specific PRO-CTCAE (Patient-Reported Outcomes- Common Terminology Criteria for Adverse Events)
To assess patient-reported treatment tolerability in high-risk NMIBC participants treated with durvalumab + BCG (induction and maintenance) combination therapy by descriptive summary of PRO-CTCAE. Percentage of all dosed participants reporting each response category of each of the 19 relevant disease symptom items as measured by PRO-CTCAE. The PRO-CTCAE system, is an item bank of symptoms experienced by participants while undergoing treatment of their cancer.
Complete response rate (CRR)
Complete response rate (CRR) is defined as the percentage of participants having carcinoma in situ (CIS) prior to study entry or at baseline cystoscopy who do not have CIS at 6 months.
Disease-free survival (DFS)
Disease-free survival (DFS) is defined as the time from the date of first dose of study intervention until the date of first recurrence of high-risk disease or death (by any cause in the absence of recurrence) regardless of whether the participant withdraws from therapy or receives another anticancer therapy prior to recurrence.
Overall survival (OS)
Overall survival (OS) is defined as the time from the date of the first dose of study intervention to the date of death from any cause. The analysis will include all dosed participants. All deaths will be included regardless of whether the participant withdraws from therapy or receives another anticancer therapy.
Best overall response for health-related quality of life (HRQoL) as assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items (EORTC QLQ-C30)
Best overall response is defined as the best response the participant achieved, based on evaluable data collected during the study period to assess disease and treatment related symptoms and HRQoL. The domains/scales of the EORTC QLQ-C30 prioritized include global HRQoL, physical functioning and fatigue. Final scores range from 0 to 100, where higher scores on the global measure of health status and functional scales indicate better health status/function, but higher scores on symptom scales represent greater symptom severity.
Best overall response for HRQoL as assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Non-Muscle-Invasive Bladder Cancer 24 (EORTC QLQ-NMIBC24)
Best overall response is defined as the best response the participant achieved, based on evaluable data collected during the study period. The domains/scales of the EORTC QLQ-NMIBC24 prioritized include urinary symptoms, intravesical treatment concerns, future perspectives and sexual functioning. Final scores range from 0 to 100, higher scores on the functioning scales (sexual functioning, sexual enjoyment) indicate better health status/function, whereas higher scores on symptom scales and individual symptom items represent greater symptom severity.

Full Information

First Posted
July 5, 2023
Last Updated
August 23, 2023
Sponsor
AstraZeneca
Collaborators
Parexel
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1. Study Identification

Unique Protocol Identification Number
NCT05943106
Brief Title
BCG in Combination With Durvalumab in Adult BCG-naïve, High-risk NMIBC Participants
Acronym
PATAPSCO
Official Title
A Phase IIIb Open-Label, Single-Arm, Multi-Center, US Study of Bacillus Calmette-Guerin (BCG) Administered in Combination With Durvalumab in Adult BCG-naïve, High-risk Non-Muscle- Invasive Bladder Cancer Participants (PATAPSCO)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 11, 2023 (Actual)
Primary Completion Date
August 31, 2025 (Anticipated)
Study Completion Date
December 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
Collaborators
Parexel

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to assess the safety, tolerability, and efficacy profile of durvalumab + BCG (induction and maintenance) combination therapy in adult United States participants with a histologically confirmed diagnosis of high-risk non-muscle-invasive bladder cancer (NMIBC), who have received no prior systemic therapy for NMIBC, and who are BCG-naïve.
Detailed Description
This is an open-label, single-arm, multi-center, Phase IIIb US study exploring the combination of durvalumab and BCG (induction and maintenance) in participants with high-risk NMIBC. Each participant will have screening activities up to 4 weeks before initiation of study intervention, receive study intervention for up to 24 months, followed by 3 months safety follow-up. Participants will continue to be followed up for survival until 2 years from the date of treatment initiation of the last participant enrolled in this study (approximately 42 months after first participant enrolled).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Muscle- Invasive Bladder Cancer
Keywords
Bacillus Calmette-Guerin (BCG), BCG-naïve, immunotherapeutics, human mAb, Durvalumab, non-muscle-invasive bladder cancer (NMIBC)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Durvalumab + BCG
Arm Type
Experimental
Arm Description
Participants will receive Durvalumab for 13 cycles every 4 weeks (q4w) for a maximum 12 months. All participants will receive BCG (supplied by the site) intravesically, as induction weekly for 6 weeks. Patients will subsequently receive BCG for maintenance for 3 weekly doses at 3,6,12,18, and up to 24 months, at the physician's discretion.
Intervention Type
Biological
Intervention Name(s)
Durvalumab
Intervention Description
Participants will receive Durvalumab via intravenous infusion from Week 1 for 13 cycles every 4 weeks (q4w) for maximum 12 months.
Intervention Type
Biological
Intervention Name(s)
BCG
Intervention Description
Participants will receive BCG via intravesical as induction weekly for 6 weeks starting at Week 1, Day 1 and subsequently for maintenance for 3 weekly doses up to 3, 6, 12, 18, and 24 months, at the physician's discretion as Standard of care.
Primary Outcome Measure Information:
Title
Incidence of Grade 3 or 4 Possibly related adverse events (PRAEs)
Description
A PRAE is defined as an AE that has been assessed by the Investigator to be possibly related to study treatment. A PRAE will be included if it has onset or worsens (by Investigator report of an increase in CTCAE (common terminology criteria for adverse events) grade relative to pre-treatment) within 6 months of initiation of study intervention and it has CTCAE Grade 3 or 4 recorded within this timeframe.
Time Frame
From the date of the first dose of study treatment (Day 1) until 6 months after the initiation of study treatment
Secondary Outcome Measure Information:
Title
Number of participants with adverse events (AEs)
Description
To further assess the safety and tolerability of durvalumab + BCG (induction and maintenance) combination therapy in high risk NMIBC participants. Number of participants with adverse events (AEs), including PRAEs, adverse events of special interest (AESIs), immune-mediated AEs, serious adverse events (SAEs), AEs resulting in treatment interruption and discontinuation will be assessed.
Time Frame
From screening (Day -28 to -1) until 90 days following discontinuation of the last dose of study treatment (approximately 28 months)
Title
Percentage of patient-reported treatment tolerability symptoms assessed using specific PRO-CTCAE (Patient-Reported Outcomes- Common Terminology Criteria for Adverse Events)
Description
To assess patient-reported treatment tolerability in high-risk NMIBC participants treated with durvalumab + BCG (induction and maintenance) combination therapy by descriptive summary of PRO-CTCAE. Percentage of all dosed participants reporting each response category of each of the 19 relevant disease symptom items as measured by PRO-CTCAE. The PRO-CTCAE system, is an item bank of symptoms experienced by participants while undergoing treatment of their cancer.
Time Frame
Up to 24 months
Title
Complete response rate (CRR)
Description
Complete response rate (CRR) is defined as the percentage of participants having carcinoma in situ (CIS) prior to study entry or at baseline cystoscopy who do not have CIS at 6 months.
Time Frame
At 6 months
Title
Disease-free survival (DFS)
Description
Disease-free survival (DFS) is defined as the time from the date of first dose of study intervention until the date of first recurrence of high-risk disease or death (by any cause in the absence of recurrence) regardless of whether the participant withdraws from therapy or receives another anticancer therapy prior to recurrence.
Time Frame
At 12 months and 24 months
Title
Overall survival (OS)
Description
Overall survival (OS) is defined as the time from the date of the first dose of study intervention to the date of death from any cause. The analysis will include all dosed participants. All deaths will be included regardless of whether the participant withdraws from therapy or receives another anticancer therapy.
Time Frame
At 24 months
Title
Best overall response for health-related quality of life (HRQoL) as assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items (EORTC QLQ-C30)
Description
Best overall response is defined as the best response the participant achieved, based on evaluable data collected during the study period to assess disease and treatment related symptoms and HRQoL. The domains/scales of the EORTC QLQ-C30 prioritized include global HRQoL, physical functioning and fatigue. Final scores range from 0 to 100, where higher scores on the global measure of health status and functional scales indicate better health status/function, but higher scores on symptom scales represent greater symptom severity.
Time Frame
Up to 24 months
Title
Best overall response for HRQoL as assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Non-Muscle-Invasive Bladder Cancer 24 (EORTC QLQ-NMIBC24)
Description
Best overall response is defined as the best response the participant achieved, based on evaluable data collected during the study period. The domains/scales of the EORTC QLQ-NMIBC24 prioritized include urinary symptoms, intravesical treatment concerns, future perspectives and sexual functioning. Final scores range from 0 to 100, higher scores on the functioning scales (sexual functioning, sexual enjoyment) indicate better health status/function, whereas higher scores on symptom scales and individual symptom items represent greater symptom severity.
Time Frame
Up to 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
130 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: BCG-naïve (defined as participants not having received prior intravesical BCG or who previously received but stopped BCG more than 3 years before study entry). Local histological confirmation (based on cytology and/or pathology report) of high-risk transitional cell carcinoma of the urothelium of the urinary bladder confined to the mucosa or submucosa. Complete resection of all Ta/T1 papillary disease prior to enrollment, with the transurethral resection of bladder tumor (TURBT) removing high-risk NMIBC (non-muscle invasive bladder cancer) performed not more than 4 months before enrollment in the study. No prior radiotherapy for bladder cancer. A life expectancy of at least 12 weeks (90 days). Adequate organ and marrow function World Health Organization/Eastern Cooperative Oncology Group performance status of 0 or 1 at screening No prior exposure to immune-mediated therapy of cancer A candidate for BCG treatment. Local histological confirmation (based on cytology and/or pathology report) of high-risk transitional cell carcinoma of the urothelium of the urinary bladder confined to the mucosa or submucosa. A high-risk tumor is defined as one of the following: T1 tumor; High-grade/G3 tumor; CIS. Exclusion Criteria: Evidence of muscle-invasive, locally advanced, metastatic, and/or extra-vesical bladder cancer (ie, T2, T3, T4, and / or Stage IV). Predominantly variant histology such as micropapillary, plasmacytoid, nested, sarcomatoid, microcystic, squamous and adeno variants of UC representing > 50% of tumor tissue or other than urothelial tumors as assessed by pathology. Evidence of lymphovascular invasion of bladder tumor, except if treatment with BCG is deemed to be the only clinically viable treatment. Immediate cystectomy is indicated. Known or documented absolute and/or relative contraindication of adjuvant intravesical BCG treatment. Concurrent extravesical, non-muscle-invasive transitional cell carcinoma of the urothelium. History of allogenic organ transplantation. Participants with any history of allogenic stem cell transplantation are also excluded. Active or prior documented autoimmune or inflammatory disorders. Participants with hypothyroidism stable on hormone replacement. History of active primary immunodeficiency. Active infection including hepatitis B (known positive HBV/HBsAg result), HCV, or HIV 1/2 (positive HIV) antibodies. Current or prior use of immunosuppressive medication within 14 days before the first durvalumab dose. Female participants who are pregnant or breastfeeding or male or female participants of reproductive potential who are not willing to employ highly effective birth control. Any concurrent chemotherapy, study intervention, biologic or hormonal therapy for cancer treatment; uncontrolled intercurrent illness; History of another primary malignancy except for Malignancy treated with curative intent and with no known active disease ≥ 2 years; Adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease; Adequately treated CIS without evidence of disease; Prostate cancer of stage ≤ T2cN0M0 without biochemical recurrence or progression that in the opinion of the Investigator does not require active intervention. Previous or concurrent treatment with potent systemic immunostimulatory agents
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
AstraZeneca Clinical Study Information Center
Phone
1-877-240-9479
Email
information.center@astrazeneca.com
Facility Information:
Facility Name
Research Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Conway
State/Province
Arkansas
ZIP/Postal Code
72034
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Greenwood
State/Province
Indiana
ZIP/Postal Code
46143
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67226
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21203
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Hanover
State/Province
Maryland
ZIP/Postal Code
21076
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Voorhees
State/Province
New Jersey
ZIP/Postal Code
08043
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
Myrtle Beach
State/Province
South Carolina
ZIP/Postal Code
29572
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37209
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Austin
State/Province
Texas
ZIP/Postal Code
78745
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Spokane
State/Province
Washington
ZIP/Postal Code
99202
Country
United States
Individual Site Status
Not yet recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
IPD Sharing Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing Access Criteria
When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home

Learn more about this trial

BCG in Combination With Durvalumab in Adult BCG-naïve, High-risk NMIBC Participants

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