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). 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 treatment in the maintenance treatment period at Months 6, 9 and 12. The study duration is 24 months.
- Drug: ALT-803BCG and ALT-803 will be mixed together (with saline) and administered via intravesical instillation weekly for 6 consecutive weeks (induction). 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 treatment in the maintenance treatment period at Months 6, 9 and 12.
- Drug: BCGBCG and ALT-803 will be mixed together (with saline) and administered via intravesical instillation weekly for 6 consecutive weeks (induction). 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 treatment in the maintenance treatment period at Months 6, 9 and 12.
|Ages eligible for Study||18 Years and older|
|Genders eligible for Study||All|
|Accepts Healthy Volunteers||No|
- 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
- Histologically confirmed presence of CIS (with or without Ta or T1 disease) or histologically confirmed presence of high-grade Ta or T1 disease (without CIS)
- 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)
- BCG-unresponsive disease as defined as: (a) Persistent high-grade disease or recurrence within 6 months of receiving at least two courses of intravesical BCG (at least five of six induction doses and at least two of three maintenance doses); or (b) T1 high-grade disease at the first evaluation following induction BCG alone (at least 5 of six induction doses)
- 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
- Recurrence > 6 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
- Evidence of muscle-invasive or regional and/or distant metastatic bladder cancer
- New York Heart Association (NYHA) Class III or IV heart failure or other clinical signs of severe cardiac dysfunction
- Symptomatic congestive heart failure (CHF), 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.
United States (14)
- Alaska Clinical Research CenterrecruitingAnchorage, Alaska, United States, 99503
- UCLA Department of UrologyrecruitingLos Angeles, California, United States, 90024
- Skyline UrologyrecruitingSherman Oaks, California, United States, 91411
- Skyline UrologyrecruitingTorrance, California, United States, 90505
- Urology AssociatesrecruitingEnglewood, Colorado, United States, 80113
- Eastern Connecticut Hematolgoy and Oncology AssociatesrecruitingNorwich, Connecticut, United States, 06360
- University of Miami Miller School of Medicine-Sylvester Comprehensive Cancer CenterrecruitingMiami, Florida, United States, 33136
- University of Hawaii Cancer CenterrecruitingHonolulu, Hawaii, United States, 96814
- Karmanos Cancer Institutenot yet recruitingDetroit, Michigan, United States, 48201
- Roswell Park Cancer Insitutenot yet recruitingBuffalo, New York, United States, 14263
- Winthrop University Hospital Department of UrologyrecruitingGarden City, New York, United States, 11530
- Clinical Research Solutionsnot yet recruitingMiddleburg Heights, Ohio, United States, 44130
- Vanderbilt University Medical Centernot yet recruitingNashville, Tennessee, United States, 37232
- Madigan Army Medical Centernot yet recruitingTacoma, Washington, United States, 98431
01 June, 2017
09 November, 2017