A Phase 1/2 Study of HS-410 in Patients With Non-Muscle Invasive Bladder Cancer After TURBT

Bladder Cancer Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02010203
• Other study ID #: HS410-101
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: December 2013
• Est. completion date: April 2018

Study information

• Verified date: February 2020
• Source: Heat Biologics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 104
• Est. completion date: April 2018
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Biological:
• HS-410
Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
• Placebo
Injection containing sterile solution but no cells
• BCG
Vaccine derived from a live bacterium

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland
United States	Montefiore Medical Center	Bronx	New York
United States	University of North Carolina Chapel Hill	Chapel Hill	North Carolina
United States	University of Chicago	Chicago	Illinois
United States	Urology of North Texas	Dallas	Texas
United States	Urology Center of Colorado	Denver	Colorado
United States	MD Anderson Cancer Center	Houston	Texas
United States	First Urology	Jeffersonville	Indiana
United States	Horizon Oncology Research	Lafayette	Indiana
United States	University of California at Los Angeles	Los Angeles	California
United States	University of Minnesota	Minneapolis	Minnesota
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Skyline Urology	Sherman Oaks	California
United States	Skyline Urology	Torrance	California
United States	Urology of Virginia	Virginia Beach	Virginia
United States	University of Kansas Cancer Center	Westwood	Kansas
United States	University of Massachusetts	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Heat Biologics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Safety and Tolerability	To evaluate the safety and tolerability of vesigenurtacel-L	Up to 3 years.
Primary	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	One year
Secondary	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	Up to 2 years
Secondary	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	Up to 2 years
Secondary	Disease-free Survival at 3, 6, 18, and 24 Months	Evaluate Disease Free Survival at 3, 6, 18 and 24 months	Up to 2 years
Secondary	Overall Disease-free Survival	Evaluate overall Disease Free Survival	Up to 3 years
Secondary	Overall Survival, Expressed as the Number of Participants Alive	Evaluate overall survival (OS)	Up to 3 years
Secondary	Proportion of Patients Undergoing Repeat Transurethral Resection of Bladder Tumor (TURBT) by 12 and 24 Months		Up to 2 years
Secondary	Proportion of Patients Undergoing Cystectomy by 12 and 24 Months	Evaluate the proportion of patients undergoing cystectomy by 12 and 24 months from randomization	Up to 2 years
Secondary	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	Up to 2 years
Secondary	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 (IFN?) and granzyme B (gzB)	Up to 3 years
Secondary	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)	Up to 3 years
Secondary	Tumor Antigen Expression	Evaluation of pre-treatment tumor tissue for antigen expression	At screening
Secondary	Tumor Infiltrating Lymphocytes (TILs)	Evaluation of tumor tissue obtained from repeat biopsy, if clinically indicated, for presence of TILs	Up to 3 years
Secondary	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.	Up to 2 years
Secondary	Safety of the Combination of the HS-410 and BCG	Phase 2 only Evaluate the safety of the combination of vesigenurtacel-L and BCG	Up to 1 year
Secondary	Safety of the High Dose HS-410 Monotherapy	Phase 2 only Evaluate the safety of high dose vesigenurtacel-L monotherapy	Up to 3 years.