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

Status: Active

Description

This is a Phase II, open-label, single-arm, multicenter study of intravesical BCG plus ALT-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 ALT-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.

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.
  • 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.

Locations & Contacts

California

Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: Active
Name Not Available

Florida

Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: Active
Name Not Available
Tampa
Moffitt Cancer Center
Status: Active
Name Not Available

Hawaii

Honolulu
University of Hawaii Cancer Center
Status: Active
Contact: Isobel Webster
Phone: 808-564-5805
Email: IWebster@cc.hawaii.edu

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: Temporarily closed to accrual
Name Not Available

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: Active
Name Not Available

New Hampshire

Lebanon
Dartmouth Hitchcock Medical Center
Status: In review
Name Not Available

New York

Buffalo
Roswell Park Cancer Institute
Status: Active
Name Not Available

North Carolina

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: Active
Name Not Available

Pennsylvania

Philadelphia
Thomas Jefferson University Hospital
Status: Active
Name Not Available

Tennessee

Nashville
Vanderbilt University / Ingram Cancer Center
Status: Active
Name Not Available

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Altor BioScience

Trial IDs

Primary ID CA-ALT-803-01-16
Secondary IDs NCI-2017-02022
Clinicaltrials.gov ID NCT03022825