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QUILT-3.032: A Multicenter Clinical Trial of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 in Patients With BCG Unresponsive High Grade Non-Muscle Invasive Bladder Cancer

NCT03022825

Description:

This is a Phase II/III, open-label, single-arm, multicenter study of intravesical BCG plus N-803 in patients with BCG unresponsive high grade non-muscle invasive bladder cancer (NMIBC). All patients treated in the study will receive via a urinary catheter in the bladder, BCG plus N-803 weekly for 6 consecutive weeks (initial induction treatment period). After the first disease assessment, eligible patients will receive either a 3-week maintenance course or a 6-week re-induction course (second treatment period) at Month 3. Eligible patients will continue to receive maintenance treatment in the third treatment period at Months 6, 9, 12, and 18. The study duration is 24 months.

Related Conditions:
  • Non-Muscle Invasive Bladder Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: QUILT-3.032: A Multicenter Clinical Trial of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 in Patients With BCG Unresponsive High Grade Non-Muscle Invasive Bladder Cancer
  • Official Title: QUILT-3.032: A Multicenter Clinical Trial of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 in Patients With BCG Unresponsive High Grade Non-Muscle Invasive Bladder Cancer

Clinical Trial IDs

  • ORG STUDY ID: CA-ALT-803-01-16
  • NCT ID: NCT03022825

Conditions

  • Bladder Cancer

Interventions

DrugSynonymsArms
N-803 and BCGBCG+N-803
N-803BCG+N-803

Purpose

This is a Phase II/III, open-label, single-arm, multicenter study of intravesical BCG plus N-803 in patients with BCG unresponsive high grade non-muscle invasive bladder cancer (NMIBC). All patients treated in the study will receive via a urinary catheter in the bladder, BCG plus N-803 weekly for 6 consecutive weeks (initial induction treatment period). After the first disease assessment, eligible patients will receive either a 3-week maintenance course or a 6-week re-induction course (second treatment period) at Month 3. Eligible patients will continue to receive maintenance treatment in the third treatment period at Months 6, 9, 12, and 18. The study duration is 24 months.

Trial Arms

NameTypeDescriptionInterventions
BCG+N-803Experimental
  • N-803 and BCG
  • N-803

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female patients 18 years of age or older

          -  Histologic confirmation of non-muscle invasive bladder cancer of the transitional cell
             carcinoma high-grade subtype (mixed histology tumors allowed if transitional cell
             histology is predominant histology).

          -  Histologically confirmed presence of BCG-unresponsive CIS (with or without Ta or T1
             disease) or histologically confirmed presence of BCG-unresponsive high-grade Ta or T1
             disease.

          -  Absence of resectable disease after transurethral resection (TURBT) procedures
             (residual carcinoma in situ (CIS) acceptable; patients with T1 tumors must undergo
             repeat resection and biopsy [inclusive of muscularis propria] if initial biopsy did
             not include muscularis propria). Patients with high-grade Ta and/or T1 disease should
             have complete resection before study treatment.

          -  BCG-unresponsive disease as defined as: (a) Persistent or recurrent CIS (+/- recurrent
             Ta/T1 disease) within 12 months of receiving adequate BCG (at least five of six doses
             doses of an initial induction course plus either at least two of three doses of
             maintenance therapy or at least two of six doses of a second induction course); or (b)
             Recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG (at
             least five of six doses of an initial induction course plus either at least two of
             three doses of maintenance therapy or at least two of six doses of a second induction
             course); or (c) T1 high-grade disease at the first evaluation following an induction
             BCG course alone (at least five of six doses of an initial induction course).

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

          -  Voluntary written informed consent and HIPAA authorization and agree to comply with
             all protocol-specified procedures and follow-up evaluations

        Exclusion Criteria:

          -  Recurrence of BCG unresponsive Ta/T1 disease (without presence of CIS) > 6 months
             after last BCG instillation or BCG unresponsive CIS > 12 months after last BCG
             instillation.

          -  Life expectancy <2 years

          -  Any of the following clinical laboratory values at the time of enrollment: (1)
             Absolute neutrophil count (ANC) <800/µL or (2) Platelets < 50,000/µL

          -  Liver function abnormalities as indicated by ongoing hepatic enzyme elevation (AST or
             ALT) >2 times upper limit of normal (ULN)

          -  Renal insufficiency as indicated by a creatinine level >3 times ULN

          -  History of or evidence of muscle-invasive, locally advanced, metastatic and/or
             extravesical bladder cancer; or any other cancer within the past 5 years, except:
             adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer,
             adequately treated stage I or II cancer from which the patient is currently in
             complete remission, or stable prostate cancer (under active surveillance or hormone
             control).

          -  Symptomatic congestive heart failure (CHF), New York Heart Association (NYHA) Class
             III or IV heart failure or other clinical signs of severe cardiac dysfunction

          -  Severe/unstable angina pectoris, or myocardial infarction within 6 months prior to
             study entry

          -  History or evidence of uncontrollable central nervous system (CNS) disease

          -  Active systemic infection requiring parenteral antibiotic therapy. All prior
             infections must have resolved following optimal therapy

          -  Concurrent febrile illness, active urinary tract infection, active tuberculosis, a
             history of hypotension or anaphylactic reactions

          -  Ongoing chronic systemic steroid therapy required (>10 mg oral prednisone daily or
             equivalent)

          -  Women who are pregnant or nursing. Female patients of childbearing potential must have
             a negative pregnancy test and must adhere to using a medically acceptable method of
             birth control prior to screening and agree to continue its use during the study and
             for 30 days after the last dose of study drug, or be surgically sterilized (e.g.,
             hysterectomy or tubal ligation). Women of childbearing potential are defined as any
             female who has experienced menarche and who is NOT permanently sterile or
             postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses
             without an alternative medical cause. Males must agree to use barrier methods of birth
             control while on study and for 90 days post last dose of study drug.

          -  Patients currently receiving investigational or commercial anti-cancer agents or
             anti-cancer therapies other than BCG, ALT-803 and supportive care therapies for active
             disease.

          -  Concurrent use of other investigational agents

          -  Other illness or condition, including laboratory abnormalities, which in the opinion
             of the Investigator would exclude the patient from participating in this study. This
             includes, but is not limited to, serious medical conditions or psychiatric illness
             likely to interfere with participation in the study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete Response
Time Frame:24 Months
Safety Issue:
Description:Cohort A & Cohort C: Assess incidence of complete response of CIS (with or without Ta/T1 papillary disease) patients at any time

Secondary Outcome Measures

Measure:Response
Time Frame:24 months
Safety Issue:
Description:Cohort A & Cohort C: Assess duration of complete response Cohort B: Assess disease-free survival
Measure:Response
Time Frame:6 months
Safety Issue:
Description:Cohort A & Cohort C: Assess complete response rate at 6 months. Cohort B: Assess disease-free rate at 6 months
Measure:Response
Time Frame:9 months
Safety Issue:
Description:Cohort A & Cohort C: Assess complete response rate at 9 months. Cohort B: Assess disease-free rate at 9 months
Measure:Response
Time Frame:12 months
Safety Issue:
Description:Cohort A & Cohort C: Assess complete response rate at 12 months. Cohort B: Assess disease-free rate at 12 months
Measure:Response
Time Frame:18 months
Safety Issue:
Description:Cohort A & Cohort C: Assess complete response rate at 18 months. Cohort B: Assess disease-free rate at 18 months
Measure:Response
Time Frame:24 months
Safety Issue:
Description:Cohort A & Cohort C: Assess complete response rate at 24 months. Cohort B: Assess disease-free rate at 24 months
Measure:Complete Response
Time Frame:24 months
Safety Issue:
Description:Assess complete response rate at any time of CIS patients per central pathology review Duration of complete response (all recurrent bladder cancer, including low grade Ta disease)

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:ImmunityBio, Inc.

Trial Keywords

  • BCG
  • bladder cancer
  • immunotherapy
  • interleukin-15
  • intravesical
  • non-muscle invasive
  • NMIBC

Last Updated

March 11, 2021