Open Actively Recruiting

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

About

Brief Summary

The purpose of this research study is to find out if the study drug, ALT-803, plus BCG can stop the growth of tumor in patients with non-muscle invasive bladder cancer whose tumor persisted after treatment with BCG. The sponsor also wish to collect some other information that will help them to improve the way study drug is given to patients.

In this research study, ALT-803 will be tested with BCG.

Patient will have a complete physical exam and vital signs including height, weight, heart and breathing rate, blood pressure and temperature will be checked. About two teaspoons of blood will be collected for testing the functions of patient's kidneys, liver and other organs and for blood cell counts. We will also collect urine for routine urine tests. An electrocardiogram (EKG) will be run to test electrical activity of patient's heart. The patient's lung functions will be examined if it is indicated, and will need to have a biopsy of patient's tumor tissue within 6 weeks of study entry to check the status of the disease. We also need to collect some tissue from these biopsies. The tissue may be analyzed for genes, gene products, proteins, or makers involved in cancer, interleukin response or cell death. The tissue from patient's biopsies that are collected for testing will be analyzed and stored for possible future analysis. Results from these screening tests will be used by the study doctor to find out if the patient qualifies for the research study. If the patient is a woman who can have children, we will collect another teaspoon of blood for a pregnancy test. The study doctor or study staff will tell the patient if the pregnancy test results are positive. The results of the pregnancy test must be negative in order for you to be in the study. We will enroll the patient and schedule their visits to receive the study treatment within 14 days. If the screening tests show that the patient is not eligible to continue in the research study, then the patient may not take part.

Patient's participation in the study will include one cycle of study treatment consisting of six weekly doses of BCG plus ALT-803 study drug and every 3 months visits to evaluate their response to the study treatment. Participants will receive 4 cycles of 3 weekly doses of BCG plus ALT-803 every 3 months if there is no tumor growth. Participants will receive another cycle of study treatment consisting of six weekly doses of BCG plus ALT-803 if there is a decrease in amount of cancer (residual tumor) at 3 months, followed by 4 cycles of 3 weekly doses of BCG plus ALT-803 every 3 months if there is no tumor growth in follow ups. If there is no decrease in the amount of cancer in after one cycle of treatment (6 weeks), patients will not receive more doses of study treatment.

Patient will be closely monitored during the entire treatment period. This study will last as long as patient does not have unacceptable side effects. After the patient completes the study treatment period, if they received at least one dose of study treatment, we will continue to monitor and follow the patients disease and health status every 3 months during years 1 and 2 by scheduled office visits

Primary Purpose
Treatment
Study Type
Interventional
Phase
Phase II

Eligibility

Gender
All
Healthy Volunteers
No
Minimum Age
18 Years
Maximum Age
N/A

Subjects diagnosed with a type of non-muscle invasive bladder cancer (NMIBC) and when previously treated with Bacillus Calmette-Guerin (BCG), a standard therapy for NMIBC had a limited or no response to the treatment (BCG unresponsive) For more information about the eligibility criteria for this trial, refer to the Health Professional version.

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.

Join this Trial

Contact our clinical trial navigators for opportunities that may be suitable for you
Study Stats
Protocol No.
17-000291
Category
Oncology
Urology
Location
  • UCLA Westwood
For Providers
NCT No.
NCT03022825
For detailed technical eligibility, visit ClinicalTrials.gov.