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A Study of Intravesical BCG in Combination With ALT-803 in Patients With Non-Muscle Invasive Bladder Cancer

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ClinicalTrials.gov Identifier: NCT02138734
Recruitment Status : Active, not recruiting
First Posted : May 15, 2014
Last Update Posted : September 21, 2018
Sponsor:
Information provided by (Responsible Party):
Altor BioScience

Brief Summary:
This is a Phase Ib/IIb, randomized, open-label, multicenter study of intravesical ALT-803 plus BCG versus BCG alone, in BCG naïve patients with high-grade NMIBC.

Condition or disease Intervention/treatment Phase
Non-muscle Invasive Bladder Cancer Biological: BCG+ALT-803 Biological: BCG Phase 1 Phase 2

Detailed Description:

The study includes a dose escalation phase (phase Ib) and an expansion phase (phase IIb).

In the phase Ib, patients will be treated with intravesical ALT-803 in combination with BCG. The purpose of the phase Ib portion of the study is to evaluate the safety, identify the Maximum Tolerated Dose (MTD) of ALT-803 and determine the Recommended Dose (RD) level of ALT-803 in combination with BCG for the phase IIb expansion.

In the phase IIb expansion, patients will be randomized to receive either intravesical ALT-803 in combination with BCG or BCG alone.

The purpose of the phase IIb portion of the study is to compare disease response, recurrence and survival rates, safety and quality of life between the two treatment groups.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 256 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Single arm phase Ib; two-arm phase IIb, 1:1 randomization and stratification by bladder tumor disease stage.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Study of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 in Patients With Non-Muscle Invasive Bladder Cancer
Study Start Date : July 2014
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : October 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer

Arm Intervention/treatment
Experimental: ALT-803+BCG
(Phase Ib and IIb) for BCG-naive patients
Biological: BCG+ALT-803

BCG and ALT-803 will be mixed together (with saline) and administered via intravesical instillation weekly for 6 consecutive weeks for induction. Phase IIb includes maintenance treatment consisting of BCG+ALT-803 for 3 consecutive weeks at 3, 6, 12, & 18 months.

An additional 6 week re-induction of BCG+ALT-803 for patients with eligible disease at 3 months in phase IIb is included.


Active Comparator: BCG alone
(Phase IIb) for BCG-naive patients
Biological: BCG

BCG will be administered via intravesical instillation weekly for 6 consecutive weeks for induction. Phase IIb includes maintenance treatment consisting of BCG for 3 consecutive weeks at 3, 6, 12, & 18 months.

An additional 6 week re-induction of BCG for patients with eligible disease at 3 months in phase IIb is included.





Primary Outcome Measures :
  1. Safety Profile [ Time Frame: 48 months ]
    For phase Ib and IIb Number and severity of treatment related AEs that occur or worsen after the first dose of study treatment.

  2. MTD Determination [ Time Frame: 9 months ]
    For phase Ib Determine the maximum tolerated dose (MTD)

  3. Time to Recurrence [ Time Frame: 48 months ]
    For phase IIb Assess time from first treatment to evidence of disease.

  4. RD Designation [ Time Frame: 9 months ]
    For phase Ib designate the recommended dose (RD) level for Phase IIb.


Secondary Outcome Measures :
  1. Clinical Benefit [ Time Frame: 24 months ]
    For phase Ib and IIb Assess disease response rate.

  2. Pharmacokinetics [ Time Frame: 24 months ]
    For phase Ib Area under the plasma concentration-time curve from time zero to infinity (AUC).

  3. Biomarkers [ Time Frame: 24 months ]
    For phase Ib Measures the serum and urine levels of IL-2, IL-4, IL-6, IL-10, IFN-gamma and TNF-alpha in treated patients.

  4. Molecular Alterations [ Time Frame: 24 months ]
    For phase Ib Measures the molecular changes (angiogenesis, apoptosis and proliferative index) and immune cell infiltration (assessed by immunohistochemistry for immune cells) in treated patients.

  5. Immune Cell Assessment [ Time Frame: 24 months ]
    For phase Ib Determine the percentage of specific immune cell subsets.

  6. Immunogenicity [ Time Frame: 24 months ]
    For phase Ib and IIb Measures the serum level of anti-ALT-803 in patient samples.

  7. Survival [ Time Frame: 24 months ]
    For phase Ib and IIb All enrolled patients will be followed for 2 years to determine survival.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

ENTRY CRITERIA:

DISEASE CHARACTERISTICS:

  • Histologic confirmation of non-muscle invasive bladder cancer of the transitional cell carcinoma high-grade subtype.

    • Patients are eligible if the diagnostic biopsy was done within 3 months of treatment start and a cystoscopy demonstrating no resectable disease was done within 6 weeks of treatment start. Patients with high-grade Ta and/or T1 disease should have complete resection before study treatment.
    • Upper tract imaging within 6 months prior to study entry must not be suspicious for upper tract malignancy.
  • No history of or evidence of muscle-invasive, locally advanced, metastatic and/or extravesical bladder cancer or presence of any other cancer.

PRIOR/CONCURRENT THERAPY:

  • No prior BCG treatment or known hypersensitivity to BCG. Patients who have received more than a single-dose post-operative treatment of mitomycin-C or gemcitabine are excluded.
  • No concurrent use of other investigational agents.

PATIENT CHARACTERISTICS:

Performance Status • ECOG 0, 1, or 2. Bone Marrow Reserve

  • Absolute neutrophil count (AGC/ANC) ≥ 1,000/uL
  • Platelets ≥ 100,000/uL
  • Hemoglobin ≥ 8g/dL Renal Function
  • Glomerular Filtration Rate (GFR) > 40mL/min or serum creatinine ≤ 1.5 x ULN Hepatic Function
  • Total bilirubin ≤ 2.0 X ULN
  • AST, ALT, ALP ≤ 3.0 X ULN Cardiovascular
  • No symptomatic congestive heart failure Class III or IV.
  • No severe/unstable angina pectoris < 6 months.
  • No myocardial infarction < 6 months. Pulmonary
  • Adequate pulmonary function without any clinical sign of severe pulmonary dysfunction.

Other

  • Currently eligible for intravesical BCG therapy.
  • Negative serum pregnancy test if female and of childbearing potential.
  • No women who are pregnant or nursing.
  • Subjects, both females and males, with reproductive potential must agree to use effective contraceptive measures for the duration of the study.
  • No known positive HIV status.
  • No history or evidence of uncontrollable CNS disease.
  • No psychiatric illness/social situation that would limit compliance with study requirements.
  • No other illness that in the opinion of the investigator would exclude the patient from participating in this study.
  • Must provide signed informed consent and HIPPA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations.
  • No active systemic infection requiring parenteral antibiotic therapy.
  • No ongoing chronic systemic steroid therapy required.
  • No concurrent febrile illness, active urinary tract infection, active tuberculosis, a history of hypotension or anaphylactic reactions.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02138734


Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Alaska
Alaska Clinical Research Center
Anchorage, Alaska, United States, 99503
United States, California
UCLA Department of Urology
Los Angeles, California, United States, 90024
University of California, Davis
Sacramento, California, United States, 95817
Skyline Sherman Oaks
Sherman Oaks, California, United States, 91411
Skyline Urology
Torrance, California, United States, 90505
United States, Connecticut
Eastern Connecticut Hematology & Oncology Associates
Norwich, Connecticut, United States, 06360
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Hawaii
University of Hawaii Cancer Center
Honolulu, Hawaii, United States, 96813
United States, Kansas
Kansas University Medical Center
Westwood, Kansas, United States, 66205
United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New York
Winthrop University Hospital
Mineola, New York, United States, 11501
United States, Washington
University of Washington School of Medicine
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Altor BioScience
Investigators
Study Director: Amy Rock, PhD Altor BioScience

Responsible Party: Altor BioScience
ClinicalTrials.gov Identifier: NCT02138734     History of Changes
Other Study ID Numbers: CA-ALT-803-01-14; QUILT-2.005
First Posted: May 15, 2014    Key Record Dates
Last Update Posted: September 21, 2018
Last Verified: September 2018

Keywords provided by Altor BioScience:
antitumor
BCG
bladder cancer
cancer
immunotherapy
instillation
interleukin-15
intravesical
naive
non-muscle invasive
transitional cell carcinoma
ALT-803

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases