Clinical Trials /

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

NCT02138734

Description:

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.

Related Conditions:
  • Bladder Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: QUILT-2.005: A Study of Intravesical BCG in Combination With ALT-803 in Patients With Non-Muscle Invasive Bladder Cancer
  • Official Title: A Study of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 in Patients With Non-Muscle Invasive Bladder Cancer

Clinical Trial IDs

  • ORG STUDY ID: CA-ALT-803-01-14
  • NCT ID: NCT02138734

Conditions

  • Non-muscle Invasive Bladder Cancer

Interventions

DrugSynonymsArms
BCG+ALT-803BCG+ALT-803 (phase I and II)
BCGBCG alone (phase II only)

Purpose

This is a Phase Ib/II, open-label, dose-finding, multicenter study of intravesical BCG plus ALT-803 in Non-muscle invasive bladder cancer.

Detailed Description

      The purpose of this 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 combined with BCG
      in patients who have nonmuscle invasive bladder cancer. The anti-tumor activity of
      BCG+ALT-803 will also be assessed. In addition, the study will characterize the molecular,
      immunogenicity and pharmacokinetic profile of BCG+ALT-803.

      The study includes a dose escalation phase (Phase Ib) and an expansion phase (Phase II). The
      dose escalation phase is concluded when the MTD is determined. A dose level (RD) will be
      designated for the phase II study. For the noncomparative randomized phase II, patients will
      be randomized to two treatment arms: either ALT-803 at the RD level in combination with BCG
      (50 mg) or BCG (50 mg) alone.
    

Trial Arms

NameTypeDescriptionInterventions
BCG+ALT-803 (phase I and II)Experimentalfor BCG-naive patients
    BCG alone (phase II only)Active Comparatorfor BCG-naive patients

      Eligibility Criteria

              ENTRY CRITERIA:
      
              DISEASE CHARACTERISTICS:
      
                -  Histologic confirmation of non-muscle invasive bladder cancer of the transitional cell
                   carcinoma high-risk subtype.
      
                   ◦High risk is defined as any high-grade Ta or T1, CIS.
      
                -  No evidence of muscle-invasive bladder cancer or regional and/or distant metastasis.
      
              PRIOR/CONCURRENT THERAPY:
      
                -  No prior BCG treatment.
      
                -  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 < 6 months.
      
                -  No severe/unstable angina pectoris < 6 months.
      
                -  No myocardial infarction < 6 months.
      
                -  No NYHA Class > II.
      
                -  No marked baseline prolongation of QT/QTc interval.
      
              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 autoimmune disease other than corrected hypothyroidism (for phase Ib only).
      
                -  No prior organ allograft or allogeneic transplantation (for phase Ib only).
      
                -  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.
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Safety Profile
      Time Frame:48 months
      Safety Issue:
      Description:Number and severity ot treatment related AEs that occur or worsen after the first dose of study treatment.

      Secondary Outcome Measures

      Measure:Clinical Benefit
      Time Frame:48 months
      Safety Issue:
      Description:Number of patients with an objective, complete response.
      Measure:Pharmacokinetics
      Time Frame:48 months
      Safety Issue:
      Description:For phase Ib and II Area under the plasma concentration-time curve from time zero to infinity (AUC) and the half-life of ALT-803.
      Measure:Biomarkers
      Time Frame:48 months
      Safety Issue:
      Description:Measures the serum and urine levels of IL-2, IL-4, IL-6, IL-10, IFN-gamma and TNF-alpha in treated patients.
      Measure:Molecular Alterations
      Time Frame:48 months
      Safety Issue:
      Description:Measures the molecular changes (angiogenesis, apoptosis and proliferative index) and immune cell infiltration (assessed by immunohistochemistry for immune cells) in treated patients.
      Measure:Immune Cell Assessment
      Time Frame:48 months
      Safety Issue:
      Description:The percentage and numbers of specific immune cell subsets and their phenotypes, including T cells, B cells, and NK cells will be assessed.
      Measure:Immunogenicity
      Time Frame:48 months
      Safety Issue:
      Description:Measures the serum level of anti-ALT-803 in patient samples.
      Measure:Overall Survival
      Time Frame:24 months
      Safety Issue:
      Description:All enrolled patients will have a cystoscopy and biopsy (if warranted) performed every 3 months for 2 years to determine recurrence-free survival, progression-free survival, overall survival and duration of response.

      Details

      Phase:Phase 1/Phase 2
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:Altor BioScience

      Trial Keywords

      • antitumor
      • BCG
      • bladder cancer
      • cancer
      • immunotherapy
      • instillation
      • interleukin-15
      • intravesical
      • naive
      • non-muscle invasive
      • transitional cell carcinoma

      Last Updated

      August 14, 2017