Back to resultsA Phase 1/2 Study of HS-410 in Patients With Non-Muscle Invasive Bladder Cancer After TURBT
Primary Purpose
Bladder Cancer
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
HS-410
Placebo
BCG
Sponsored by
About this trial
This is an interventional treatment trial for Bladder Cancer focused on measuring TURBT, Bladder, Cancer, GP96, Vaccine, Immunotherapy, Heat Biologics, BCG, Bacillus Calmette-Guerin, Bacillus Calmette-Guérin
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed non-muscle invasive bladder cancer [Ta, T1 or Tis (CIS)] that has been removed by transurethral resection
- Either: (i) high-risk disease, defined as T1 and/or high-grade and/or CIS or (ii) intermediate-risk disease, defined as Ta low-grade with at least 3 of the following 4 risk factors: multiple tumors, tumor size > 3cm, early recurrence (<1 year from previous staging procedure), or recurrence with a frequency of more than once in any 12 month period
- Not have received bacillus Calmette-Guérin (BCG) or have completed previous BCG treatment > 12 months prior to the baseline staging procedure.
- Phase 2 Arms 1-3: Suitable to receive a 6-week course of BCG in the adjuvant setting within 6 weeks following TURBT. Phase 2 Arm 4: Suitable for monotherapy vaccine administration post-TURBT. For Phase 1 only: Has previously received 3-6 weekly doses of BCG.
- Adequate laboratory parameters
Exclusion Criteria:
- Human immunodeficiency virus (HIV) infection or immunodeficiency disorders, either primary or acquired
- Infections or intercurrent illness requiring active therapy
- Any condition requiring active steroid or other immunosuppressive therapy
- Active malignancies within the past 12 months except negligible risk of metastasis or death treated with expected curative outcome.
- Prostate pelvic radiation within the past 12 months
- Significant cardiac impairment
- Current alcohol or chemical abuse, or mental or psychiatric condition precluding protocol compliance
- Pregnant or nursing
- Allergy to soy, egg, or peanut products
- Receiving another investigational agent (30 day wash-out required prior to first dose)
- Neo-adjuvant therapy prior to baseline staging procedures for the current occurrence of non-muscle invasive bladder cancer
- Prior treatment with a cancer vaccine for this indication
- Prior vaccination with BCG for tuberculosis disease
- Prior splenectomy
Sites / Locations
- University of California at Los Angeles
- Skyline Urology
- Skyline Urology
- Urology Center of Colorado
- University of Chicago
- First Urology
- Horizon Oncology Research
- University of Kansas Cancer Center
- Johns Hopkins University
- University of Massachusetts
- University of Minnesota
- Washington University School of Medicine
- Montefiore Medical Center
- University of North Carolina Chapel Hill
- Thomas Jefferson University
- Carolina Urologic Research Center
- Urology of North Texas
- MD Anderson Cancer Center
- Urology of Virginia
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Experimental
Arm Label
Phase I: HS-410 Low Dose
Phase II: HS-410 Low-Dose Plus BCG
Phase II: High-Dose HS-410 Plus BCG
Phase II: Placebo Plus BCG
Phase II: High-Dose HS-410
Arm Description
In the open label Phase 1 portion, HS-410 is given as 1*10^6 cells per dose for 12 weekly injections followed by 3 monthly injections.
In the Phase 2 portion, HS-410 is given as 1*10^6 cells per dose weekly for 6 weeks in combination with BCG, followed by 6 weeks of HS-410 alone, and then 3 courses of three once-weekly doses of HS-410 in combination with BCG.
In the Phase 2 portion, HS-410 is given as 1*10^7 cells per dose weekly for 6 weeks in combination with BCG, followed by 6 weeks of HS-410 alone, and then 3 courses of three once-weekly doses of HS-410 in combination with BCG.
In the Phase 2 portion, a placebo is given weekly for 6 weeks in combination with BCG, followed by 6 weeks of placebo alone, and then 3 courses of three once-weekly doses of placebo in combination with BCG.
In the Phase II portion, if patients will not receive BCG, HS-410 is given as 1*10^7 cells per dose weekly for 12 weeks, and then 3 courses of three once-weekly doses of HS-410.
Outcomes
Primary Outcome Measures
Phase 1: Safety and Tolerability
To evaluate the safety and tolerability of vesigenurtacel-L
Phase 2: 1-year Disease-Free Survival
Arm 1, 2, 3: 1-year DFS in patients with NMIBC treated with BCG in combination with blinded study product (one of two doses of vesigenurtacel-L or placebo) Arm 4: 1-year DFS in patients with NMIBC treat1fv 9 with high dose vesigenurtacel-L monotherapy
One-year disease-free survival will be defined as the proportion of patients who are free from recurrent disease, progressive disease, and alive one year after the date of randomization/treatment assignment
Secondary Outcome Measures
Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months
Evaluate the proportion of patients with recurrence at 3, 6, 12, 18, and 24 months
Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months
Evaluate the proportion of patients with progressive disease at 3, 6, 12, 18, and 24
Disease-free Survival at 3, 6, 18, and 24 Months
Evaluate Disease Free Survival at 3, 6, 18 and 24 months
Overall Disease-free Survival
Evaluate overall Disease Free Survival
Overall Survival, Expressed as the Number of Participants Alive
Evaluate overall survival (OS)
Proportion of Patients Undergoing Repeat Transurethral Resection of Bladder Tumor (TURBT) by 12 and 24 Months
Proportion of Patients Undergoing Cystectomy by 12 and 24 Months
Evaluate the proportion of patients undergoing cystectomy by 12 and 24 months from randomization
Immunologic Response of PBMCs Via Intracellular Cytokine Staining (ICS) by Flow Cytometry and/or Enzyme-linked Immunosorbent Spot (ELISPOT) on CD8+ Cells After HS-410 Vaccination as Compared to Baseline.
Evaluate the proportion of patients with immunologic response of peripheral blood mononuclear cells (PBMCs) via intracellular cytokine staining (ICS) by flow cytometry and/or ELISPOT on CD8+ cells following vesigenurtacel-L vaccination
Immunologic Response of Peripheral Blood Mononuclear Cells (PBMCs) and Stimulation Analysis Via ICS in Baseline and Post-treatment Biopsies, if Clinically Indicated
Evaluate immunologic response of PBMCs (analysis of surface markers, CD3, CD4, CD8, CD19, CD25, CD45, CD56, FoxP3, and degranulation) and stimulation analysis via ICS of interferon gamma (IFNγ) and granzyme B (gzB)
Total PBMC Counts by Flow Cytometry
Evaluate total PBMC counts by flow cytometry, including lymphocyte subsets (B cells, helper T-cells, cytotoxic T-cells, natural killer (NK) cells and T-reg)
Tumor Antigen Expression
Evaluation of pre-treatment tumor tissue for antigen expression
Tumor Infiltrating Lymphocytes (TILs)
Evaluation of tumor tissue obtained from repeat biopsy, if clinically indicated, for presence of TILs
T Cell Receptor Sequencing of Peripheral Blood T Cells Before and During Treatment
Evaluation of tumor tissue obtained from repeat biopsy, if clinically indicated, for presence of TILs, T cell receptor sequencing of peripheral blood T cells before and during the course of treatment.
Safety of the Combination of the HS-410 and BCG
Phase 2 only Evaluate the safety of the combination of vesigenurtacel-L and BCG
Safety of the High Dose HS-410 Monotherapy
Phase 2 only Evaluate the safety of high dose vesigenurtacel-L monotherapy
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02010203
Brief Title
A Phase 1/2 Study of HS-410 in Patients With Non-Muscle Invasive Bladder Cancer After TURBT
Official Title
Phase 1/2, Placebo-Controlled, Randomized Study to Evaluate the Safety, Immune Response & Clinical Activity of HS-410 in Patients With Non-Muscle Invasive Bladder Cancer Who Have Undergone Transurethral Resection of Bladder Tumor (TURBT)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Terminated
Why Stopped
Inability to accrue due to changing treatment landscape (PD-1 approvals)
Study Start Date
December 2013 (undefined)
Primary Completion Date
December 2017 (Actual)
Study Completion Date
April 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Heat Biologics
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Phase I/II study: Phase 1 is an open-label, safety study, patients who previously received 3-6 instillations of weekly intravesical Bacillus Calmette-Guerin (BCG) induction therapy (as standard of care) followed by low dose intradermal (1*10^6 cells) HS-410 monotherapy. Phase 2, patients will be randomized to one of three blinded (physician-patient), placebo-controlled groups and receive either intradermal placebo or low dose (1*10^6 cells) or high dose (1*10^7 cells) vesigenurtacel-L in combination with induction and maintenance intravesical BCG. Patients who do not receive BCG will be enrolled into an open-label, non-randomized group receiving high dose (1*10^7 cells) intradermal HS-410 monotherapy.
Detailed Description
This study is a two part study: Phase I and Phase II. The Phase 1 portion is an open-label, safety study. Patients will have previously received 3-6 instillations of weekly intravesical Bacillus Calmette-Guerin (BCG) induction therapy (as standard of care) followed by low dose intradermal (1*10^6 cells) HS-410 monotherapy. In Phase 2, patients will be assigned to treatment groups based on whether they will receive induction BCG in the typical post-TURBT window. If the investigator plans to administer BCG, patients will be randomized to one of three blinded (physician-patient), placebo-controlled groups and receive either intradermal placebo or low dose (1*10^6 cells) or high dose (1*10^7 cells) vesigenurtacel-L in combination with induction and maintenance intravesical BCG. If patients will not receive BCG, they will be enrolled into an open-label, non-randomized group and receive high dose (1*10^7 cells) intradermal HS-410 monotherapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer
Keywords
TURBT, Bladder, Cancer, GP96, Vaccine, Immunotherapy, Heat Biologics, BCG, Bacillus Calmette-Guerin, Bacillus Calmette-Guérin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
104 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase I: HS-410 Low Dose
Arm Type
Experimental
Arm Description
In the open label Phase 1 portion, HS-410 is given as 1*10^6 cells per dose for 12 weekly injections followed by 3 monthly injections.
Arm Title
Phase II: HS-410 Low-Dose Plus BCG
Arm Type
Experimental
Arm Description
In the Phase 2 portion, HS-410 is given as 1*10^6 cells per dose weekly for 6 weeks in combination with BCG, followed by 6 weeks of HS-410 alone, and then 3 courses of three once-weekly doses of HS-410 in combination with BCG.
Arm Title
Phase II: High-Dose HS-410 Plus BCG
Arm Type
Experimental
Arm Description
In the Phase 2 portion, HS-410 is given as 1*10^7 cells per dose weekly for 6 weeks in combination with BCG, followed by 6 weeks of HS-410 alone, and then 3 courses of three once-weekly doses of HS-410 in combination with BCG.
Arm Title
Phase II: Placebo Plus BCG
Arm Type
Placebo Comparator
Arm Description
In the Phase 2 portion, a placebo is given weekly for 6 weeks in combination with BCG, followed by 6 weeks of placebo alone, and then 3 courses of three once-weekly doses of placebo in combination with BCG.
Arm Title
Phase II: High-Dose HS-410
Arm Type
Experimental
Arm Description
In the Phase II portion, if patients will not receive BCG, HS-410 is given as 1*10^7 cells per dose weekly for 12 weeks, and then 3 courses of three once-weekly doses of HS-410.
Intervention Type
Biological
Intervention Name(s)
HS-410
Intervention Description
Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Injection containing sterile solution but no cells
Intervention Type
Biological
Intervention Name(s)
BCG
Other Intervention Name(s)
Bacillus Calmette-Guerin
Intervention Description
Vaccine derived from a live bacterium
Primary Outcome Measure Information:
Title
Phase 1: Safety and Tolerability
Description
To evaluate the safety and tolerability of vesigenurtacel-L
Time Frame
Up to 3 years.
Title
Phase 2: 1-year Disease-Free Survival
Description
Arm 1, 2, 3: 1-year DFS in patients with NMIBC treated with BCG in combination with blinded study product (one of two doses of vesigenurtacel-L or placebo) Arm 4: 1-year DFS in patients with NMIBC treat1fv 9 with high dose vesigenurtacel-L monotherapy
One-year disease-free survival will be defined as the proportion of patients who are free from recurrent disease, progressive disease, and alive one year after the date of randomization/treatment assignment
Time Frame
One year
Secondary Outcome Measure Information:
Title
Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months
Description
Evaluate the proportion of patients with recurrence at 3, 6, 12, 18, and 24 months
Time Frame
Up to 2 years
Title
Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months
Description
Evaluate the proportion of patients with progressive disease at 3, 6, 12, 18, and 24
Time Frame
Up to 2 years
Title
Disease-free Survival at 3, 6, 18, and 24 Months
Description
Evaluate Disease Free Survival at 3, 6, 18 and 24 months
Time Frame
Up to 2 years
Title
Overall Disease-free Survival
Description
Evaluate overall Disease Free Survival
Time Frame
Up to 3 years
Title
Overall Survival, Expressed as the Number of Participants Alive
Description
Evaluate overall survival (OS)
Time Frame
Up to 3 years
Title
Proportion of Patients Undergoing Repeat Transurethral Resection of Bladder Tumor (TURBT) by 12 and 24 Months
Time Frame
Up to 2 years
Title
Proportion of Patients Undergoing Cystectomy by 12 and 24 Months
Description
Evaluate the proportion of patients undergoing cystectomy by 12 and 24 months from randomization
Time Frame
Up to 2 years
Title
Immunologic Response of PBMCs Via Intracellular Cytokine Staining (ICS) by Flow Cytometry and/or Enzyme-linked Immunosorbent Spot (ELISPOT) on CD8+ Cells After HS-410 Vaccination as Compared to Baseline.
Description
Evaluate the proportion of patients with immunologic response of peripheral blood mononuclear cells (PBMCs) via intracellular cytokine staining (ICS) by flow cytometry and/or ELISPOT on CD8+ cells following vesigenurtacel-L vaccination
Time Frame
Up to 2 years
Title
Immunologic Response of Peripheral Blood Mononuclear Cells (PBMCs) and Stimulation Analysis Via ICS in Baseline and Post-treatment Biopsies, if Clinically Indicated
Description
Evaluate immunologic response of PBMCs (analysis of surface markers, CD3, CD4, CD8, CD19, CD25, CD45, CD56, FoxP3, and degranulation) and stimulation analysis via ICS of interferon gamma (IFNγ) and granzyme B (gzB)
Time Frame
Up to 3 years
Title
Total PBMC Counts by Flow Cytometry
Description
Evaluate total PBMC counts by flow cytometry, including lymphocyte subsets (B cells, helper T-cells, cytotoxic T-cells, natural killer (NK) cells and T-reg)
Time Frame
Up to 3 years
Title
Tumor Antigen Expression
Description
Evaluation of pre-treatment tumor tissue for antigen expression
Time Frame
At screening
Title
Tumor Infiltrating Lymphocytes (TILs)
Description
Evaluation of tumor tissue obtained from repeat biopsy, if clinically indicated, for presence of TILs
Time Frame
Up to 3 years
Title
T Cell Receptor Sequencing of Peripheral Blood T Cells Before and During Treatment
Description
Evaluation of tumor tissue obtained from repeat biopsy, if clinically indicated, for presence of TILs, T cell receptor sequencing of peripheral blood T cells before and during the course of treatment.
Time Frame
Up to 2 years
Title
Safety of the Combination of the HS-410 and BCG
Description
Phase 2 only Evaluate the safety of the combination of vesigenurtacel-L and BCG
Time Frame
Up to 1 year
Title
Safety of the High Dose HS-410 Monotherapy
Description
Phase 2 only Evaluate the safety of high dose vesigenurtacel-L monotherapy
Time Frame
Up to 3 years.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed non-muscle invasive bladder cancer [Ta, T1 or Tis (CIS)] that has been removed by transurethral resection
Either: (i) high-risk disease, defined as T1 and/or high-grade and/or CIS or (ii) intermediate-risk disease, defined as Ta low-grade with at least 3 of the following 4 risk factors: multiple tumors, tumor size > 3cm, early recurrence (<1 year from previous staging procedure), or recurrence with a frequency of more than once in any 12 month period
Not have received bacillus Calmette-Guérin (BCG) or have completed previous BCG treatment > 12 months prior to the baseline staging procedure.
Phase 2 Arms 1-3: Suitable to receive a 6-week course of BCG in the adjuvant setting within 6 weeks following TURBT. Phase 2 Arm 4: Suitable for monotherapy vaccine administration post-TURBT. For Phase 1 only: Has previously received 3-6 weekly doses of BCG.
Adequate laboratory parameters
Exclusion Criteria:
Human immunodeficiency virus (HIV) infection or immunodeficiency disorders, either primary or acquired
Infections or intercurrent illness requiring active therapy
Any condition requiring active steroid or other immunosuppressive therapy
Active malignancies within the past 12 months except negligible risk of metastasis or death treated with expected curative outcome.
Prostate pelvic radiation within the past 12 months
Significant cardiac impairment
Current alcohol or chemical abuse, or mental or psychiatric condition precluding protocol compliance
Pregnant or nursing
Allergy to soy, egg, or peanut products
Receiving another investigational agent (30 day wash-out required prior to first dose)
Neo-adjuvant therapy prior to baseline staging procedures for the current occurrence of non-muscle invasive bladder cancer
Prior treatment with a cancer vaccine for this indication
Prior vaccination with BCG for tuberculosis disease
Prior splenectomy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gary Steinberg, MD
Organizational Affiliation
University of Chicago
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California at Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Skyline Urology
City
Sherman Oaks
State/Province
California
ZIP/Postal Code
91411
Country
United States
Facility Name
Skyline Urology
City
Torrance
State/Province
California
ZIP/Postal Code
90505
Country
United States
Facility Name
Urology Center of Colorado
City
Denver
State/Province
Colorado
ZIP/Postal Code
80211
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
First Urology
City
Jeffersonville
State/Province
Indiana
ZIP/Postal Code
47130
Country
United States
Facility Name
Horizon Oncology Research
City
Lafayette
State/Province
Indiana
ZIP/Postal Code
47905
Country
United States
Facility Name
University of Kansas Cancer Center
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
University of Massachusetts
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10471
Country
United States
Facility Name
University of North Carolina Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Carolina Urologic Research Center
City
Myrtle Beach
State/Province
South Carolina
ZIP/Postal Code
29572
Country
United States
Facility Name
Urology of North Texas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Urology of Virginia
City
Virginia Beach
State/Province
Virginia
ZIP/Postal Code
23462
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Phase 1/2 Study of HS-410 in Patients With Non-Muscle Invasive Bladder Cancer After TURBT
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