Study of Cretostimogene Given in Patients With Non-Muscle Invasive Bladder Cancer ,Unresponsive to Bacillus-Calmette-Guerin

Launched by CG ONCOLOGY, INC. · Jun 29, 2020

Keywords

ClinConnect Summary

This clinical trial is studying a treatment called Cretostimogene for patients with non-muscle invasive bladder cancer (NMIBC) who have not responded to a previous therapy called Bacillus Calmette-Guerin (BCG). Specifically, the trial is focusing on two groups of patients: those with a type of bladder cancer called carcinoma in situ (CIS) and those with high-grade papillary disease (HG Ta/T1). To participate, patients must be at least 18 years old and have had their cancer confirmed by a doctor. They should also have experienced either persistent or recurring cancer after their last BCG treatment, which must have occurred within specific time frames.

Participants in this trial can expect to receive the Cretostimogene treatment and will need to undergo regular check-ups, including bladder exams and urine tests, throughout the study. It's important to note that patients must be medically fit enough to participate and should not have other serious health issues or recent treatments that might interfere with the study. This trial aims to gather more information on how effective Cretostimogene is for these patients, helping to find better treatment options for bladder cancer in the future.

Gender

ALL

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