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

NCT ID: NCT02010203

Last Updated: 2020-02-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2018-04-30

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.

Conditions

Bladder Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Phase I: HS-410 Low Dose

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.

Group Type: EXPERIMENTAL

HS-410

Intervention Type: BIOLOGICAL

Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96

Phase II: HS-410 Low-Dose Plus BCG

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.

Group Type: EXPERIMENTAL

HS-410

Intervention Type: BIOLOGICAL

Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96

BCG

Intervention Type: BIOLOGICAL

Vaccine derived from a live bacterium

Phase II: High-Dose HS-410 Plus 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.

Group Type: EXPERIMENTAL

HS-410

Intervention Type: BIOLOGICAL

Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96

BCG

Intervention Type: BIOLOGICAL

Vaccine derived from a live bacterium

Phase II: Placebo Plus 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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Injection containing sterile solution but no cells

BCG

Intervention Type: BIOLOGICAL

Vaccine derived from a live bacterium

Phase II: High-Dose HS-410

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.

Group Type: EXPERIMENTAL

HS-410

Intervention Type: BIOLOGICAL

Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96

Interventions

HS-410

Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96

Intervention Type: BIOLOGICAL

Placebo

Injection containing sterile solution but no cells

Intervention Type: BIOLOGICAL

BCG

Vaccine derived from a live bacterium

Intervention Type: BIOLOGICAL

Other Intervention Names

Bacillus Calmette-Guerin

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Heat Biologics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gary Steinberg, MD

Role: PRINCIPAL_INVESTIGATOR

University of Chicago

Locations

University of California at Los Angeles

Los Angeles, California, United States

Skyline Urology

Sherman Oaks, California, United States

Skyline Urology

Torrance, California, United States

Urology Center of Colorado

Denver, Colorado, United States

University of Chicago

Chicago, Illinois, United States

First Urology

Jeffersonville, Indiana, United States

Horizon Oncology Research

Lafayette, Indiana, United States

University of Kansas Cancer Center

Westwood, Kansas, United States

Johns Hopkins University

Baltimore, Maryland, United States

University of Massachusetts

Worcester, Massachusetts, United States

University of Minnesota

Minneapolis, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

Montefiore Medical Center

The Bronx, New York, United States

University of North Carolina Chapel Hill

Chapel Hill, North Carolina, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

Urology of North Texas

Dallas, Texas, United States

MD Anderson Cancer Center

Houston, Texas, United States

Urology of Virginia

Virginia Beach, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

HS410-101

Identifier Type: -

Identifier Source: org_study_id