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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Heat Biologics
Sponsor:
Information provided by (Responsible Party):
Heat Biologics
ClinicalTrials.gov Identifier:
NCT02010203
First received: December 5, 2013
Last updated: August 21, 2014
Last verified: August 2014
  Purpose

This is a two-part study. The first stage will test the safety of HS-410, and the second stage will determine whether treatment with bacillus Calmette-Guérin (BCG) in combination with one of two doses of HS-410 increases disease-free survival at 1 year compared to BCG in combination with placebo.


Condition Intervention Phase
Bladder Cancer
Biological: HS-410
Biological: Placebo
Biological: BCG
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Heat Biologics:

Primary Outcome Measures:
  • Phase 1: Safety and tolerability [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
  • Phase 2: 1-year Disease-Free Survival [ Time Frame: One year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients with recurrence at 6, 12, 18, and 24 months [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Proportion of patients with progressive disease at 6, 12, 18, and 24 months [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Disease-free survival at 6, 18, and 24 months [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Overall disease-free survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Proportion of patients undergoing repeat transurethral resection of bladder tumor (TURBT) by 12 and 24 months [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Proportion of patients undergoing cystectomy by 12 and 24 months [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Immunologic response via intracellular cytokine staining (ICS) by flow cytometry and/or enzyme-linked immunosorbent spot (ELISPOT) on CD8+ cells after receiving 6 HS-410 doses, after 12 HS-410 doses, and at end of treatment as compared to baseline. [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Total PBMC counts by flow cytometry [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Tumor antigen expression [ Time Frame: At screening ] [ Designated as safety issue: No ]
    Evaluation of pre-treatment tumor tissue for antigen expression

  • Tumor Infiltrating Lymphocytes (TILs) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 84
Study Start Date: December 2013
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Biological: HS-410
Vaccine derived from irradiated urothelial bladder cancer cells genetically engineered to continually secrete gp96
Experimental: 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.
Biological: HS-410
Vaccine derived from irradiated urothelial bladder cancer cells genetically engineered to continually secrete gp96
Biological: BCG
Vaccine derived from a live bacterium
Other Name: bacillus Calmette-Guerin
Experimental: 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.
Biological: HS-410
Vaccine derived from irradiated urothelial bladder cancer cells genetically engineered to continually secrete gp96
Biological: BCG
Vaccine derived from a live bacterium
Other Name: bacillus Calmette-Guerin
Placebo Comparator: 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.
Biological: Placebo
Injection containing sterile solution but no cells
Biological: BCG
Vaccine derived from a live bacterium
Other Name: bacillus Calmette-Guerin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 TURBT), 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 most-recent TURBT
  • Suitable to receive a 6-week course of BCG in the adjuvant setting within 6 weeks following 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
  • Autoimmune syndromes, primary or acquired (History of resolved autoimmune disease is not exclusionary)
  • Other malignancies within the past 12 months except basal and/or squamous cell carcinoma(s), in situ cervical cancer, or prostate cancer that is low grade and on active surveillance or after radical prostatectomy with currently undetectable prostate specific antigen (PSA)
  • Prostate pelvic radiation within the past 12 months
  • Significant cardiac impairment
  • Current alcohol or chemical abuse, or mental or psychiatric condition precluding protocol compliance
  • 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 most-recent TURBT
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02010203

Contacts
Contact: Victoria Brown 919-794-7910 vbrown@heatbio.com

Locations
United States, California
Skyline Urology Not yet recruiting
Torrance, California, United States, 90505
Contact: Stacey Gomez    818-990-5020    stacey.gomez@skyuro.com   
Principal Investigator: Frederick Wolk, MD         
United States, Colorado
Urology Center of Colorado Recruiting
Denver, Colorado, United States, 80211
Contact: Judy Gibson    303-421-5783    jgibson@tucc.com   
Principal Investigator: Larry Karsh, MD         
United States, Illinois
University of Chicago Not yet recruiting
Chicago, Illinois, United States, 60637
Contact: MaryAnn Schroder    773-834-9198    mschroder@surgery.bsd.uchicago.edu   
Principal Investigator: Gary Steinberg, MD         
United States, Indiana
First Urology Recruiting
Jeffersonville, Indiana, United States, 47130
Contact: Christina Dallas    812-288-2611    cdallas@1sturology.com   
Principal Investigator: James Bailen, MD         
United States, Kansas
University of Kansas Cancer Center Not yet recruiting
Westwood, Kansas, United States, 66205
Contact: TBD         
Principal Investigator: Jeffery Holzbeierlein, MD         
United States, Maryland
Johns Hopkins University Not yet recruiting
Baltimore, Maryland, United States, 21287
Contact: TBD         
Principal Investigator: Trinity J Bivalacqua, MD, PhD         
United States, Massachusetts
University of Massachusetts Not yet recruiting
Worcester, Massachusetts, United States, 01655
Contact: Krystal Star    508-856-2424    krystal.starr2@umassmemorial.org   
Principal Investigator: Vijay Katsuri, MD         
United States, North Carolina
University of North Carolina Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Madeline Carroll    919-843-5199    madeline_carroll@med.unc.edu   
Principal Investigator: Michael Woods, MD         
United States, South Carolina
Carolina Urologic Research Center Recruiting
Myrtle Beach, South Carolina, United States, 29572
Contact: Michelle Allen    843-449-1010 ext 265      
Principal Investigator: Neal Shore, MD         
United States, Texas
Urology of North Texas Not yet recruiting
Dallas, Texas, United States, 75231
Contact: Sharon Reeves    214-580-1482    reeves@urologyclinics.com   
Principal Investigator: James Cochran, MD         
Sponsors and Collaborators
Heat Biologics
Investigators
Principal Investigator: Gary Steinberg, MD University of Chicago
  More Information

No publications provided

Responsible Party: Heat Biologics
ClinicalTrials.gov Identifier: NCT02010203     History of Changes
Other Study ID Numbers: HS410-101
Study First Received: December 5, 2013
Last Updated: August 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Heat Biologics:
TURBT
Bladder
Cancer
GP96
Vaccine
Immunotherapy
Heat Biologics
BCG
Bacillus Calmette-Guerin
Bacillus Calmette-Guérin

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
BCG Vaccine
Adjuvants, Immunologic
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 21, 2014