Overview

This trial is active, not recruiting.

Condition bladder cancer
Treatments hs-410, placebo, bcg
Phase phase 1/phase 2
Sponsor Heat Biologics
Start date December 2013
End date June 2016
Trial size 110 participants
Trial identifier NCT02010203, HS410-101

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
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.
hs-410
Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
(Experimental)
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.
hs-410
Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
bcg Bacillus Calmette-Guerin
Vaccine derived from a live bacterium
(Experimental)
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.
hs-410
Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
bcg Bacillus Calmette-Guerin
Vaccine derived from a live bacterium
(Placebo Comparator)
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.
placebo
Injection containing sterile solution but no cells
bcg Bacillus Calmette-Guerin
Vaccine derived from a live bacterium
(Experimental)
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.
hs-410
Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96

Primary Outcomes

Measure
Phase 1: Safety and tolerability
time frame: Up to 3 years
Phase 2: 1-year Disease-Free Survival
time frame: One year

Secondary Outcomes

Measure
Proportion of patients with recurrence at 3, 6, 12, 18, and 24 months
time frame: Up to 2 years
Proportion of patients with progressive disease at 3, 6, 12, 18, and 24 months
time frame: Up to 2 years
Disease-free survival at 3, 6, 18, and 24 months
time frame: Up to 2 years
Overall disease-free survival
time frame: Up to 3 years
Overall survival
time frame: Up to 3 years
Proportion of patients undergoing repeat transurethral resection of bladder tumor (TURBT) by 12 and 24 months
time frame: Up to 2 years
Proportion of patients undergoing cystectomy by 12 and 24 months
time frame: Up to 2 years
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.
time frame: Up to 2 years
Immunologic response of peripheral blood mononuclear cells (PBMCs) and stimulation analysis via ICS in baseline and post-treatment biopsies, if clinically indicated
time frame: Up to 3 years
Total PBMC counts by flow cytometry
time frame: Up to 3 years
Tumor antigen expression
time frame: At screening
Tumor Infiltrating Lymphocytes (TILs)
time frame: Up to 3 years
T cell receptor sequencing of peripheral blood T cells before and during treatment
time frame: Up to 2 years
Safety of the combination of the HS-410 and BCG
time frame: Up to 1 year
Safety of the high dose HS-410 monotherapy
time frame: Up to 3 years

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title A Phase 1/2, Placebo-Controlled, Randomized Study to Evaluate the Safety, Immune Response and Clinical Activity of HS-410 in Patients With Non-Muscle Invasive Bladder Cancer Who Have Undergone Transurethral Resection of Bladder Tumor (TURBT)
Principal investigator Gary Steinberg, MD
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by Heat Biologics.
Location data was received from the National Cancer Institute and was last updated in April 2016.