A Study of Intravesical BCG in Combination With ALT-803 in Patients With Non-Muscle Invasive Bladder Cancer

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02138734
• Other study ID #: CA-ALT-803-01-14; QUILT-2.005
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 21, 2014
• Est. completion date: December 2038

Study information

• Verified date: March 2024
• Source: ImmunityBio, Inc.
• Contact: Paula Bradshaw, MPH, MBA
• Phone: 844-413-8500
• Email: paula.bradshaw[@]immunitybio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

The study includes a dose escalation phase (phase Ib) and an expansion phase (phase IIb). In the phase Ib, patients will be treated with intravesical N-803 in combination with BCG. The purpose of the phase Ib portion of the study is to evaluate the safety, identify the Maximum Tolerated Dose (MTD) of N-803 and determine the Recommended Dose (RD) level of N-803 in combination with BCG for the phase IIb expansion. In the phase IIb expansion, patients will be randomized to receive either intravesical N-803 in combination with BCG or BCG alone. Patients will be enrolled into one of two study cohorts (Cohort A and Cohort B). These will be two independent study cohorts, evaluated separately for treatment efficacy.

Recruitment information / eligibility

• 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.

Related Conditions & MeSH terms

• Non-muscle Invasive Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Biological:
• BCG+N-803
BCG and N-803 will be mixed together (with saline) and administered via intravesical instillation weekly for 6 consecutive weeks for induction. Phase IIb includes maintenance treatment consisting of BCG+N-803 for 3 consecutive weeks at 3, 6, 12, 18, 24,30 and 36 months. An additional 6 week re-induction of BCG+N-803 for patients with eligible disease at 3 months in phase IIb is included.
• BCG
BCG will be administered via intravesical instillation weekly for 6 consecutive weeks for induction. Phase IIb includes maintenance treatment consisting of BCG for 3 consecutive weeks at 3, 6, 12, 18, 24, 30 and 36 months. An additional 6 week re-induction of BCG for patients with eligible disease at 3 months in phase IIb is included.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
ImmunityBio, Inc.

Country where clinical trial is conducted

United States, 

Outcome

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