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 February 2016 by Heat Biologics
Sponsor:
Information provided by (Responsible Party):
Heat Biologics
ClinicalTrials.gov Identifier:
NCT02010203
First received: December 5, 2013
Last updated: February 9, 2016
Last verified: February 2016
  Purpose
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.

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 3, 6, 12, 18, and 24 months [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Proportion of patients with progressive disease at 3, 6, 12, 18, and 24 months [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Disease-free survival at 3, 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 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 ] [ 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 ]
  • Safety of the combination of the HS-410 and BCG [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    Phase 2 only

  • Safety of the high dose HS-410 monotherapy [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    Phase 2 only


Estimated Enrollment: 110
Study Start Date: December 2013
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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. This arm is completed.
Biological: HS-410
Vaccine derived from irradiated prostate cancer cells genetically engineered to continually secrete gp96
Experimental: 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. This arm is closed to enrollment.
Biological: HS-410
Vaccine derived from irradiated prostate cancer cells genetically engineered to continually secrete gp96
Biological: BCG
Vaccine derived from a live bacterium
Other Name: Bacillus Calmette-Guerin
Experimental: 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. This arm is closed to enrollment.
Biological: HS-410
Vaccine derived from irradiated prostate cancer cells genetically engineered to continually secrete gp96
Biological: BCG
Vaccine derived from a live bacterium
Other Name: Bacillus Calmette-Guerin
Placebo Comparator: 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. This arm is closed to enrollment.
Biological: Placebo
Injection containing sterile solution but no cells
Biological: BCG
Vaccine derived from a live bacterium
Other Name: Bacillus Calmette-Guerin
Experimental: 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. This arm is open to enrollment.
Biological: HS-410
Vaccine derived from irradiated prostate cancer cells genetically engineered to continually secrete gp96

  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 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
  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

  Show 20 Study Locations
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: February 9, 2016
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 February 11, 2016