Clinical trial NCT04452591: Study of Cretostimogene Given in Patients With Non-Muscle Invasive Bladder Cancer ,Unresponsive to Bacillus-Calmette-Guerin
Official title: A Phase 3 Study of Cretostimogene Grenadenorepvec in Patients With Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus-Calmette-Guerin (BCG)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Non Muscle Invasive Bladder Cancer
High-grade Ta/ T1 Papillary Disease Bladder Cancer
Keywords: high-grade Ta papillary disease
high-grade T1 papillary disease
carcinoma in situ
Bacillus-Calmette-Guerin unresponsive
Lead sponsor: CG Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2020-06-30
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase 3, open-label, single arm trial designed to evaluate Cretostimogene patients with NMIBC who have failed prior BCG therapy. Up to approximately 115 CIS bladder cancer patients with or without HG Ta or HG T1 papillary disease will be enrolled under the original protocol through Amendment 4, which will comprise Cohort C. Cohort C is closed to enrollment.

Under Amendment 5-1, Cohort P was added to enroll up to 70 patients with HG Ta/T1 papillary bladder cancer.

Under Amendment 6, the target number of patients enrolled in Cohort P was increased to 75. Cohort P is open to enrollment

Cohort C and Cohort P will be analyzed and reported separately. Patients will have had to fail prior BCG therapy which is defined as having persistent or recurrent disease within 12 months (Cohort C) or 6 months (Cohort P) following the completion of adequate BCG therapy for HGUC

Detailed description: Cohort C(All Countries) :

An open-label trial designed to evaluate Cretostimogene + DDM in patients with NMIBC who have failed prior BCG therapy. Single treatment arm that enrolled 115 patients with carcinoma in situ with or without concomitant high-grade Ta or T1 papillary disease

BCG failure is defined as a persistent or recurrent disease within 12 months of completion of adequate BCG therapy.

Cohort P(Japan and the United States Only):

To determine the all-cause High Grade Event Free Survival (HG-EFS) of cretostimogene in up to 75 patients with BCG-unresponsive HG Ta/T1 papillary disease without CIS.

BCG failure is defined as a persistent or recurrent disease within 6 months of completion of adequate BCG therapy.

Eligibility 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 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

Primary outcomes:
measure: Cohort C:
timeFrame: 36 months
measure: Cohort P:
timeFrame: 36 months
Secondary outcomes:
measure: Cohort C: Duration of response (DOR)
timeFrame: 36 months
measure: Cohort C and Cohort P: Assess high-grade reoccurrence free survival (RFS)
timeFrame: up to 60 months
measure: Cohort C and Cohort P: Assess progression free survival (PFS )
timeFrame: up to 60 months
measure: Cohort C:Complete Response rate at 12 months
timeFrame: 12 months
measure: Cohort C and Cohort P : Cystectomy free survival
timeFrame: up to 60 months
measure: Cohort C and Cohort P: Evaluate the safety of Cretostimogene
timeFrame: 36 months
measure: Cohort C: Assess overall survival
timeFrame: up to 60 months
measure: Cohort C: Reoccurrence free survival
timeFrame: up to 60 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Cancer Center
state: Arizona
city: Tucson
country: United States
facility: Arizona Institute of Urology
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Urology
state: Arkansas
city: Irvine
country: United States
facility: University of California - Irvine
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Lakewood
country: United States
facility: Colorado Clinical Research
state: Colorado
city: Lone Tree
country: United States
facility: Urology Associates
state: Colorado
city: Washington
country: United States
facility: MedStar Hospital
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Tampa
country: United States
facility: Moffit Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Greenwood
country: United States
facility: Urology of Indiana
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas
state: Kansas
city: Wichita
country: United States
facility: Wichita Urology
state: Kansas
city: Lafayette
country: United States
facility: Southern Urology
state: Louisiana
city: Severna Park
country: United States
facility: Chesapeake Urology
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Mercy Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Saint Louis
country: United States
facility: Specialty Clinical Research of St. Louis
state: Missouri
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: Lancaster
country: United States
facility: Keystone Urology Specialists
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania, Perelman School of Medicine
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Germantown
country: United States
facility: Conrad Pearson Clinic
state: Tennessee
city: Nashville
country: United States
facility: Urology Associates- Nashville
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Houston Metro Urology
state: Texas
city: San Antonio
country: United States
facility: Urology San Antonio, PA
state: Texas
city: Spokane
country: United States
facility: Spokane Urology
state: Washington
city: Geelong
country: Australia
facility: Barwon Health, University Hospital Geelong
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
city: Wollongong
country: Australia
facility: Wollongong Private Hospital
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Fujita
country: Japan
facility: Nagoya University Hospital
city: Hashimoto
country: Japan
facility: Hirosaki University Hospital
city: Hiroshima
country: Japan
facility: Chugoku Rosai Hospital
city: Ishizuka
country: Japan
facility: Shinshu University Hospital
city: Kandori
country: Japan
facility: University of Tsukuba Hospital
city: Kashihara
country: Japan
facility: Nara Medical University Hospital
city: Kashiwa
country: Japan
facility: The Jikei University Kashiwa Hospital
city: Kikuchi
country: Japan
facility: St. Marianna University Hospital
city: Kyoto
country: Japan
facility: National Hospital Organization Kyoto Medical Center
city: Marugame
country: Japan
facility: Kagawa Rosai Hospital
city: Matsumoto
country: Japan
facility: Keio University Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: Osaka City University Hospital
city: Osaka
country: Japan
facility: Osaka Medical and Pharmaceutical University Hospital
city: Sagamihara
country: Japan
facility: Kitsato University Hospital
city: Saitama
country: Japan
facility: Saitama City Hospital
city: Sapporo
country: Japan
facility: Sapporo Medical University Hospital
city: Shizuoka
country: Japan
facility: Shizuoka General Hospital
city: Tokyo
country: Japan
facility: Keio University Hospital
city: Toon
country: Japan
facility: Ehime University Hospital
city: Toyoma
country: Japan
facility: Toyoma University Hospital
city: Wakayama
country: Japan
facility: Wakayama Medical University Hospital
city: Yokohama
country: Japan
facility: National Hospital Organization Yokohama Medical Center
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Gyeongsang
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
city: Jeongnam
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea
city: Keelung City
country: Taiwan
facility: Keelung Chang Gung Memorial Hospital
city: Keelung
country: Taiwan
facility: Keelung Chang Gung Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: CG Oncology
name: CG Oncology
role: STUDY_DIRECTOR
References: