Clinical trial NCT03022825: QUILT-3.032: A Multicenter Clinical Trial of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 (N-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 (N-803) in Patients With BCG Unresponsive High Grade Non-Muscle Invasive Bladder Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Bladder Cancer
Keywords: BCG
bladder cancer
immunotherapy
interleukin-15
intravesical
non-muscle invasive
NMIBC
Lead sponsor: ImmunityBio, Inc.
Sponsor class: INDUSTRY
First posted: 2017-01-18
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase II/III, open-label, single-arm, multicenter study of intravesical BCG plus N-803 or N-803 only 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 or N-803 only 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. Eligible patients have the option to receive maintenance treatment in the fourth treatment period at Months 24, 30, and 36. The study duration is 60 months.


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 (inclusive of the prostatic urethra); or any other cancer within the past 5 years that is progressing or requires active treatment. Exceptions are adequately treated basal cell or squamous cell skin cancer that has undergone potentially curative therapy or in situ cervical cancer; and adequately treated stage I or II cancer or stable prostate cancer from which the patient is currently in complete remission, and is 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 (not including FDA authorized drugs for the prevention and treatment of COVID-19).
* 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.

Primary outcomes:
measure: Complete Response
timeFrame: 60 Months
measure: Disease-Free Rate
timeFrame: 12 Months
Secondary outcomes:
measure: Response
timeFrame: 60 months
measure: Response
timeFrame: 6 months
measure: Response
timeFrame: 9 months
measure: Response
timeFrame: 12 months
measure: Response
timeFrame: 18 months
measure: Response
timeFrame: 24 months
measure: Complete Response
timeFrame: 60 months
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Clinical Research Center
state: Alaska
city: Little Rock
country: United States
facility: Arkansas Urology
state: Arkansas
city: Los Angeles
country: United States
facility: UCLA Department of Urology
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital
state: California
city: Sherman Oaks
country: United States
facility: Skyline Urology
state: California
city: Torrance
country: United States
facility: Skyline Urology
state: California
city: Englewood
country: United States
facility: Urology Associates, PC
state: Colorado
city: Miami
country: United States
facility: University of Miami Miller School of Medicine-Sylvester Comprehensive Cancer Center
state: Florida
city: Pompano Beach
country: United States
facility: Clinical Research Center of Florida
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Augusta
country: United States
facility: Dwight D. Eisenhower Army Medical Center
state: Georgia
city: Honolulu
country: United States
facility: University of Hawaii Cancer Center
state: Hawaii
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Omaha
country: United States
facility: Adult & Pediatric Urology
state: Nebraska
city: Albuquerque
country: United States
facility: Accument Rx
state: New Mexico
city: Buffalo
country: United States
facility: Roswell Park Cancer Insitute
state: New York
city: Garden City
country: United States
facility: Winthrop University Hospital Department of Urology
state: New York
city: New York
country: United States
facility: Integrated Medical Professionals
state: New York
city: Poughkeepsie
country: United States
facility: Premier Medical Group of the Hudson Valley
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Chapel Hill
country: United States
facility: UNC Chapel Hill
state: North Carolina
city: Raleigh
country: United States
facility: Associated Urologists of North Carolina
state: North Carolina
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Richmond
country: United States
facility: Virginia Urology
state: Virginia
city: Tacoma
country: United States
facility: Madigan Army Medical Center
state: Washington
Study officials:
affiliation: University of California, Los Angeles
name: Karim Chamie, MD
role: PRINCIPAL_INVESTIGATOR
References: