Non-muscle Invasive Bladder Cancer Clinical Trial
Official title:
A Study of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 (N-803) in Patients With Non-Muscle Invasive Bladder Cancer
This is a Phase Ib/IIb, randomized, two-cohort, open-label, multicenter study of intravesical N-803 plus BCG versus BCG alone, in BCG naïve patients with high-grade NMIBC.
Status | Recruiting |
Enrollment | 596 |
Est. completion date | December 2038 |
Est. primary completion date | December 2028 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria 1. 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). 1. Cohort A: Histologically confirmed CIS (with or without Ta/T1 disease); Cohort B: Histologically confirmed high-grade papillary disease (Ta/T1 only). 2. Patients are eligible if the diagnostic biopsy was done within 3 months of treatment start and a cystoscopy demonstrating no resectable disease was done within 90 days of treatment start (residual CIS is acceptable; patients with T1 disease must undergo repeat resection if muscularis propria is not present in each biopsy sample). Patients with high-grade Ta and/or T1 disease should have complete resection before study treatment. 3. Upper tract imaging within 6 months prior to study entry must not be suspicious for upper tract malignancy. 2. Currently eligible for intravesical BCG therapy. 3. Age = 18 years. 4. Performance status: ECOG performance status of 0, 1, or 2. 5. BCG-naive disease as defined as either of the following: 1. Have not received prior intravesical BCG; or 2. Previously received BCG, but stopped receiving more than 3 years before date of randomization. 6. Laboratory tests performed within 21 days of treatment start: 1. Absolute neutrophil count (AGC/ANC) = 1,000/µL 2. Platelets = 100,000/µL [Patients may be transfused to meet this requirement] 3. Hemoglobin = 8 g/dL [Patients may be transfused to meet this requirement] 4. Calculated glomerular filtration rate (GFR*) >40 mL/min or Serum creatinine = 1.5 x ULN 5. Total bilirubin = 2.0 X ULN 6. AST, ALT, ALP = 3.0 X ULN 7. Adequate pulmonary function without any clinical sign of severe pulmonary dysfunction. PFT > 50% FEV1 if clinically indicated by the investigator. 8. Negative serum pregnancy test if female and of childbearing potential (non-childbearing is defined as greater than one year postmenopausal or surgically sterilized). 9. Female participants of childbearing potential must adhere to using a medically accepted method of birth control prior to screening and agree to continue its use during the study or be surgically sterilized (e.g., hysterectomy or tubal ligation) and males must agree to use barrier methods of birth control while on study. 10. Provide signed informed consent and HIPPA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations. - using the following Cockcroft-Gault equation to calculate the eGFR for this study: eGFR in mL/min = {(140-age in years) x (weight in kg) x F}/(serum creatinine in mg/dL x 72) Where F =1 if male; and 0.85 if female Exclusion Criteria 1. Prior BCG treatment or known hypersensitivity to BCG. Patients who have received more than a single-dose post-operative treatment of mitomycin-C or gemcitabine following the most recent screening TURBT/biopsy are excluded. 2. Concurrent use of other investigational agents (not including FDA-authorized drugs for the prevention and treatment of COVID-19). 3. 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 1 or 2 cancer from which the patient is currently in complete remission, or stable prostate cancer (under active surveillance or hormone control). 4. Symptomatic congestive heart failure (CHF), NYHA (New York Heart Association) Class III or IV or other clinical signs of severe cardiac dysfunction. 5. Severe/unstable angina pectoris, or myocardial infarction within 6 months prior to study entry. 6. History or evidence of uncontrollable CNS disease. 7. Known HIV-positive. 8. Active systemic infection requiring parenteral antibiotic therapy. All prior infections must have resolved following optimal therapy. 9. Concurrent febrile illness, active urinary tract infection, active tuberculosis, a history of hypotension or anaphylactic reactions. 10. Ongoing chronic systemic steroid therapy required (>10 mg oral prednisone daily or equivalent). 11. 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. 12. Psychiatric illness/social situations that would limit compliance with study requirements. 13. Other illness that in the opinion of the investigator would exclude the patient from participating in this study. |
Country | Name | City | State |
---|---|---|---|
United States | Urology Group of New Mexico (AccumetRx Clinical Research) | Albuquerque | New Mexico |
United States | Alaska Clinical Research Center | Anchorage | Alaska |
United States | University of Alabama at Birmingham | Birmingham | Alabama |
United States | University of North Carolina Chapel Hill | Chapel Hill | North Carolina |
United States | Karmanos Cancer Institute | Detroit | Michigan |
United States | University of Hawaii Cancer Center | Honolulu | Hawaii |
United States | Hoag Cancer Center | Irvine | California |
United States | Dartmouth-Hitchcock Medical Center | Lebanon | New Hampshire |
United States | Arkansas Urology | Little Rock | Arkansas |
United States | UCLA Department of Urology | Los Angeles | California |
United States | Winthrop University Hospital | Mineola | New York |
United States | Manhattan Medical Research | New York | New York |
United States | Eastern Connecticut Hematology & Oncology Associates | Norwich | Connecticut |
United States | Adult & Pediatric Urology | Omaha | Nebraska |
United States | Clinical Research Center of Florida | Pompano Beach | Florida |
United States | Premier Medical Group of the Hudson Valley | Poughkeepsie | New York |
United States | Associated Urologists of North Carolina | Raleigh | North Carolina |
United States | Virginia Urology | Richmond | Virginia |
United States | University of California, Davis | Sacramento | California |
United States | University of Washington School of Medicine | Seattle | Washington |
United States | Skyline Sherman Oaks | Sherman Oaks | California |
United States | Moffitt Cancer Center | Tampa | Florida |
United States | Skyline Urology | Torrance | California |
United States | Kansas University Medical Center | Westwood | Kansas |
Lead Sponsor | Collaborator |
---|---|
ImmunityBio, Inc. |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Immunogenicity: serum level of anti-N-803 in patient samples | For phase Ib and IIb Measures the serum level of anti-N-803 in patient samples. | 36 Months | |
Primary | Complete Response (CR) Rate | For phase IIb patients in Cohort A: compare complete response rate between treatment arms using cystoscopy, confirmatory bladder biopsy and urine cytology. | 6 Months | |
Primary | Disease Free Survival (DFS) | For phase IIb patients in Cohort B: compare disease-free survival between treatment arms using cystoscopy, confirmatory bladder biopsy and urine cytology. | 36 Months | |
Secondary | Progression-free survival (PFS) | For phase IIb, Cohorts A & B: time from randomization to disease progression or death | 10 Years | |
Secondary | Overall survival | For phase Ib and IIb: all enrolled patients will be followed for 2 years to determine survival. | 10 Years | |
Secondary | Disease specific survival | For phase IIb, Cohorts A & B: time from randomization to death resulting from bladder cancer | 10 Years | |
Secondary | Time to disease worsening | For phase IIb, Cohorts A & B: cystectomy or change in therapy indicative of more advanced disease, including systemic chemotherapy or radiation therapy | 10 Years | |
Secondary | Time to cystectomy | For phase IIb, Cohorts A & B: time from randomization to cystectomy | 10 years | |
Secondary | Safety Profile: Number and severity of treatment related AEs | For phase Ib and phase IIb Number and severity of treatment related AEs that occur or worsen after the first dose of study treatment. | 39 Months |
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