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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04452591




Registration number
NCT04452591
Ethics application status
Date submitted
26/06/2020
Date registered
30/06/2020

Titles & IDs
Public title
Study of Cretostimogene Given in Patients With Non-Muscle Invasive Bladder Cancer ,Unresponsive to Bacillus-Calmette-Guerin
Scientific title
A Phase 3 Study of Cretostimogene Grenadenorepvec in Patients With Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus-Calmette-Guerin (BCG)
Secondary ID [1] 0 0
CG3002S
Universal Trial Number (UTN)
Trial acronym
BOND-003
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non Muscle Invasive Bladder Cancer 0 0
High-grade Ta/ T1 Papillary Disease Bladder Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bladder - transitional cell cancer
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Cretostimogene Grenadenorepvec
Other interventions - n-dodecyl-B-D-maltoside

Experimental: Cohort C(All Countries):Enrollment Closed - Patients with CIS with or without HG Ta/T1 papillary disease. Cretostimogene will be administered intravesically following a series of bladder washes with 5% DDM and normal saline. Cretostimogene will be administered weekly x 6 on Weeks 1, 2, 3, 4, 5, and 6. If the patient has disease recurrence at Week 13, they will receive another cycle of 6 weekly treatments. If there is no disease present at Week 13 then the patient will receive 3 weekly treatments. Cohort C(All Countries):Beginning at Week 25, patients will receive weekly x 3 treatments every 12 weeks through week 51 then every 6 months and then a last treatment at Weeks 73, 74, and 75 until the tumor returns or study treatment is completed at Week 97. Cohort C Extension( Japan and the US) At Week 25, patients will receive weekly x 3 treatments every 12 weeks through week 51 then every 6 months starting at Weeks 73, 74, and 75 through Weeks 157, 158, and 159 until the tumor returns or study treatment is completed at Week 159.

Experimental: Cohort P(Japan and United States Only) :Open to Enrollment - HG Ta/T1 papillary disease bladder cancer patients.

In Cohort P, cretostimogene will be administered at a dose of 1 × 1012vp IVE following instillation of 5% DDM. Cretostimogene will be administered every week for 6 treatments on Weeks 1, 2, 3, 4, 5, and 6. If the patient has recurrence at Week 13 or any timepoint, the patient will receive a second induction of 6 weekly treatments (Weeks 13, 14, 15, 16, 17, and 18.). If the tumor has not returned they will receive 3 weekly treatments every 12 weeks (approximately 3 months) starting Weeks 13, 14, and 15 through Week 51 (approximately 12 months), and then every 6 months starting at Weeks 73, 74, and 75 (approximately 18 months) through Month 36.


Treatment: Other: Cretostimogene Grenadenorepvec
Engineered Oncolytic Adenovirus

Other interventions: n-dodecyl-B-D-maltoside
Transduction-enhancing agent.
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cohort C:
Timepoint [1] 0 0
36 months
Primary outcome [2] 0 0
Cohort P:
Timepoint [2] 0 0
36 months
Secondary outcome [1] 0 0
Cohort C: Duration of response (DOR)
Timepoint [1] 0 0
36 months
Secondary outcome [2] 0 0
Cohort C and Cohort P: Assess high-grade reoccurrence free survival (RFS)
Timepoint [2] 0 0
up to 60 months
Secondary outcome [3] 0 0
Cohort C and Cohort P: Assess progression free survival (PFS )
Timepoint [3] 0 0
up to 60 months
Secondary outcome [4] 0 0
Cohort C:Complete Response rate at 12 months
Timepoint [4] 0 0
12 months
Secondary outcome [5] 0 0
Cohort C and Cohort P : Cystectomy free survival
Timepoint [5] 0 0
up to 60 months
Secondary outcome [6] 0 0
Cohort C and Cohort P: Evaluate the safety of Cretostimogene
Timepoint [6] 0 0
36 months
Secondary outcome [7] 0 0
Cohort C: Assess overall survival
Timepoint [7] 0 0
up to 60 months
Secondary outcome [8] 0 0
Cohort C: Reoccurrence free survival
Timepoint [8] 0 0
up to 60 months

Eligibility
Key inclusion criteria
Cohort C Inclusion Criteria

In order to be eligible for participation in this trial, the patient must:

* Be =18 years of age (or legal age of majority in the jurisdiction) on day of signing informed consent.
* Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
* Have pathologically confirmed (WHO grading system employed for tumor grading) (Compérat 2019) BCG unresponsive CIS. Patients with BCG unresponsive CIS are those unlikely to benefit from, and who will not be receiving, further intravesical BCG. There is no maximum limit to the amount of prior BCG treatment, but maintenance BCG should be administered on a schedule consistent with standard induction-maintenance protocols (e.g., BCG weekly × 6 then weekly × 3 weeks administered at Months 3, 6, 12, 18, 24, and 36). Specifically, the definition of BCG unresponsive CIS will also require the following:

* Pathologically confirmed relapsed or persistent CIS (with or without HG Ta or HG T1 disease) within 12 months of completion (last dose) of adequate BCG treatment for HGUC (e.g., CIS, HG Ta, HG T1, or a combination of these HGUC pathologies).
* Completion of qualifying BCG treatment (e.g., "5+2" minimum exposure) within 12 months of the initial qualifying dose of BCG (e.g., induction and initial maintenance or re-induction cycle must be completed over no more than a 12-month period of time).
* Pathological confirmation of BCG unresponsive CIS within 8 weeks of study enrollment.
* CIS specimen must be predominantly urothelial (transitional cell) and have less than 50% variant (e.g., sarcomatoid, squamous etc. component) histology.
* No maximum limit to the amount of BCG administered but maintenance BCG should be administered on a schedule consistent with the SWOG 8507 regimen (Lamm 2000).
* Have all Ta and/or T1 disease resected and all CIS resected or fulgurated, as feasible, prior to study treatment (e.g., prior to Day 1 treatment).
* Ineligible to receive radical cystectomy (medically unfit) or refusal of radical cystectomy according to Investigator assessment.
* Demonstrate adequate organ function
* Patients must be willing to comply with study mandated cystoscopies, urine cytology, urograms, biopsies, and other procedures (including TURBT or other resection for all Ta/T1 disease) for the duration of the study. Patients who withdraw consent for these procedures will be withdrawn from the trial

Cohort P Inclusion Criteria

* Be =18 years of age (or legal age of majority in the jurisdiction) on day of signing informed consent
* Have ECOG performance status of 0 to 2.
* Have pathologically confirmed (WHO grading system employed for tumor grading) (Compérat 2019) BCG-unresponsive HG Ta/T1 papillary disease without CIS. Patients with BCG-unresponsive HG Ta/T1 papillary disease are those unlikely to benefit from and who will not be receiving further IVE BCG. There is no maximum limit to the amount of prior BCG treatment, but maintenance BCG should be administered on a schedule consistent with standard induction-maintenance protocols. Specifically, the definition of BCG unresponsive HG Ta/T1 papillary disease without CIS will also require the following:

* Pathologically confirmed recurrent HG Ta/T1 papillary disease without CIS within 6 months of completion (last dose) of adequate BCG treatment for HGUC (e.g., CIS, HG Ta, HG T1, or a combination of these HGUC pathologies).
* Patients with HG Ta: Completion of qualifying BCG treatment (e.g., "5+2" minimum exposure) within 12 months of the initial qualifying dose of BCG (e.g., induction and initial maintenance or re-induction cycle must be completed over no more than a 12-month period of time).
* Patients with HG T1: Patients may be eligible after the initial induction alone (5 of 6 doses of an induction course) as the qualifying BCG treatment.
* Completion (last dose) of qualifying BCG treatment within 12 months of study enrollment.
* Pathological confirmation of BCG-unresponsive HG Ta/T1 papillary disease without CIS within 14 days of study enrollment.
* All pathology specimens must be predominantly urothelial (transitional cell) and have less than 50% variant (e.g., sarcomatoid, squamous etc. component) histology.
* No maximum limit to the amount of BCG administered; however, there should be no more than 12 months between cycles of BCG
* Have all Ta and/or T1 disease resected, prior to study treatment (e.g., prior to Day 1 treatment).
* Ineligible to receive radical cystectomy (medically unfit) or refusal of radical cystectomy based on Investigator assessment.
* Demonstrate adequate organ function,
* Patients must be willing to comply with study-mandated cystoscopies, urine cytology, imaging, biopsies, and other procedures for the duration of the trial

Cohort C and Cohort P Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has current or past history of muscle invasive (T2 or higher stage) or locally advanced (T3/T4, any N) or metastatic bladder cancer.
* Any HGUC as T1, HG Ta, or CIS in the upper genitourinary tract or prostatic urethra (including CIS of the urethra) within 24 months prior to enrollment OR any history of T2 or higher stage urothelial carcinoma in the upper genitourinary tract (kidneys, renal collecting systems, ureters).
* Has received systemic anti-cancer therapy, including investigational agents, within 4 weeks of Day 1.
* Has had prior systemic treatment (with the exception of checkpoint inhibitor therapy), radiation therapy, or surgery for bladder cancer other than TURBT or bladder biopsies.
* Has any of the following within the 6 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, pulmonary embolus, uncontrolled hypertension, or uncontrolled congestive heart failure.
* Cannot tolerate study-related biopsies, IVE administration, or 1-hour bladder hold of cretostimogene.
* IVE therapy within 8 weeks prior to beginning study treatment with the exception of cytotoxic agents (e.g., Mitomycin C, gemcitabine, doxorubicin and epirubicin) when administered as a single instillation immediately following a TURBT procedure which is permitted 14 or more days prior to beginning study treatment

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/10/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
24/12/2029
Actual
Sample size
Target
190
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Barwon Health, University Hospital Geelong - Geelong
Recruitment hospital [2] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment hospital [3] 0 0
Wollongong Private Hospital - Wollongong
Recruitment postcode(s) [1] 0 0
- Geelong
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- Wollongong
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
South Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Washington
Country [19] 0 0
Japan
State/province [19] 0 0
Chiba
Country [20] 0 0
Japan
State/province [20] 0 0
Fujita
Country [21] 0 0
Japan
State/province [21] 0 0
Hashimoto
Country [22] 0 0
Japan
State/province [22] 0 0
Hiroshima
Country [23] 0 0
Japan
State/province [23] 0 0
Ishizuka
Country [24] 0 0
Japan
State/province [24] 0 0
Kandori
Country [25] 0 0
Japan
State/province [25] 0 0
Kashihara
Country [26] 0 0
Japan
State/province [26] 0 0
Kashiwa
Country [27] 0 0
Japan
State/province [27] 0 0
Kikuchi
Country [28] 0 0
Japan
State/province [28] 0 0
Kyoto
Country [29] 0 0
Japan
State/province [29] 0 0
Marugame
Country [30] 0 0
Japan
State/province [30] 0 0
Matsumoto
Country [31] 0 0
Japan
State/province [31] 0 0
Okayama
Country [32] 0 0
Japan
State/province [32] 0 0
Osaka
Country [33] 0 0
Japan
State/province [33] 0 0
Sagamihara
Country [34] 0 0
Japan
State/province [34] 0 0
Saitama
Country [35] 0 0
Japan
State/province [35] 0 0
Sapporo
Country [36] 0 0
Japan
State/province [36] 0 0
Shizuoka
Country [37] 0 0
Japan
State/province [37] 0 0
Tokyo
Country [38] 0 0
Japan
State/province [38] 0 0
Toon
Country [39] 0 0
Japan
State/province [39] 0 0
Toyoma
Country [40] 0 0
Japan
State/province [40] 0 0
Wakayama
Country [41] 0 0
Japan
State/province [41] 0 0
Yokohama
Country [42] 0 0
Korea, Republic of
State/province [42] 0 0
Busan
Country [43] 0 0
Korea, Republic of
State/province [43] 0 0
Goyang-si
Country [44] 0 0
Korea, Republic of
State/province [44] 0 0
Gyeongsang
Country [45] 0 0
Korea, Republic of
State/province [45] 0 0
Jeongnam
Country [46] 0 0
Korea, Republic of
State/province [46] 0 0
Seoul
Country [47] 0 0
Taiwan
State/province [47] 0 0
Keelung City
Country [48] 0 0
Taiwan
State/province [48] 0 0
Keelung
Country [49] 0 0
Taiwan
State/province [49] 0 0
Taichung
Country [50] 0 0
Taiwan
State/province [50] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
CG Oncology, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
CG Oncology
Address 0 0
CG Oncology
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
JoAnn Horn
Address 0 0
Country 0 0
Phone 0 0
516-456-1415
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04452591