Clinical trial NCT02010203: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Bladder Cancer
Keywords: TURBT
Bladder
Cancer
GP96
Vaccine
Immunotherapy
Heat Biologics
BCG
Bacillus Calmette-Guerin
Bacillus Calmette-Guérin
Lead sponsor: Heat Biologics
Sponsor class: INDUSTRY
First posted: 2013-12-12
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Phase 1: Safety and Tolerability
timeFrame: Up to 3 years.
measure: Phase 2: 1-year Disease-Free Survival
timeFrame: One year
Secondary outcomes:
measure: Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months
timeFrame: Up to 2 years
measure: Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months
timeFrame: Up to 2 years
measure: Disease-free Survival at 3, 6, 18, and 24 Months
timeFrame: Up to 2 years
measure: Overall Disease-free Survival
timeFrame: Up to 3 years
measure: Overall Survival, Expressed as the Number of Participants Alive
timeFrame: Up to 3 years
measure: Proportion of Patients Undergoing Repeat Transurethral Resection of Bladder Tumor (TURBT) by 12 and 24 Months
timeFrame: Up to 2 years
measure: Proportion of Patients Undergoing Cystectomy by 12 and 24 Months
timeFrame: Up to 2 years
measure: 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.
timeFrame: Up to 2 years
measure: Immunologic Response of Peripheral Blood Mononuclear Cells (PBMCs) and Stimulation Analysis Via ICS in Baseline and Post-treatment Biopsies, if Clinically Indicated
timeFrame: Up to 3 years
measure: Total PBMC Counts by Flow Cytometry
timeFrame: Up to 3 years
measure: Tumor Antigen Expression
timeFrame: At screening
measure: Tumor Infiltrating Lymphocytes (TILs)
timeFrame: Up to 3 years
measure: T Cell Receptor Sequencing of Peripheral Blood T Cells Before and During Treatment
timeFrame: Up to 2 years
measure: Safety of the Combination of the HS-410 and BCG
timeFrame: Up to 1 year
measure: Safety of the High Dose HS-410 Monotherapy
timeFrame: Up to 3 years.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California at Los Angeles
state: California
city: Sherman Oaks
country: United States
facility: Skyline Urology
state: California
city: Torrance
country: United States
facility: Skyline Urology
state: California
city: Denver
country: United States
facility: Urology Center of Colorado
state: Colorado
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Jeffersonville
country: United States
facility: First Urology
state: Indiana
city: Lafayette
country: United States
facility: Horizon Oncology Research
state: Indiana
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Chapel Hill
state: North Carolina
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Dallas
country: United States
facility: Urology of North Texas
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Virginia Beach
country: United States
facility: Urology of Virginia
state: Virginia
Study officials:
affiliation: University of Chicago
name: Gary Steinberg, MD
role: PRINCIPAL_INVESTIGATOR
References: