Study of CG0070 Given in Patients With Non-Muscle Invasive Bladder Cancer ,Unresponsive to Bacillus-Calmette-Guerin

Study Overview
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Brief Summary
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To evaluate the activity of intravesical (IVE) administration of CG0070 in patients with tissue pathology confirmed non-muscular invasive bladder cancer (NMIBC) who have Bacillus-Calmette-Guerin (BCG) unresponsive disease, with either carcinoma in situ with or without Ta/T1 disease

Detailed Description
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An open-label trial designed to evaluate CG0070 + DDM in patients with NMIBC who have failed prior BCG therapy. Single treatment arm that will enroll up to 110 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.

Official Title
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A Phase 3 Study of CG0070 in Patients With Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus-Calmette-Guerin (BCG)

Conditions
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Non Muscular Invasive Bladder Cancer

Intervention / Treatment
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* Biological: CG0070
* Other: n-dodecyl-B-D-maltoside


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 Have pathologically confirmed World Health Organization (WHO) grading system employed for tumor grading) high-risk NMIBC unresponsive to prior BCG therapy defined as: Persistent or recurrent CIS alone or with recurrent Ta/T1 (noninvasive papillary disease/tumor invades the subepithelial connective tissue) disease within 12 months of completion of adequate BCG therapy Received prior adequate BCG therapy as defined as at least one of the following (5+2 minimum exposure): At least five of six doses of an initial induction course (adequate induction) plus at least two of three doses of maintenance therapy, OR At least five of six doses of an initial induction course (adequate induction) plus at least two of six doses of a second induction course. Ineligible for radical cystectomy or refusal of radical cystectomy Adequate organ function Key Exclusion Criteria: Muscle invasive (T2 or higher stage) or locally advanced (T3/T4, any N) or metastatic bladder cancer Has known upper tract or prostatic urethra malignancy Has systemic anti-cancer therapy, including investigational agents, within 4 weeks of Baseline Immuno-deficient due to chronic steroid or other immunosuppressant use, HIV, or prior organ transplant Prior treatment with adenovirus-based cancer therapy Clinically significant or active cardiac disease Active autoimmune disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br>Patients with carcinoma in situ with or without concomitant high-grade Ta or T1 papillary disease. CG0070 will be administered intravesically (IVE) following a sequence of bladder washes with 5% DDM and normal saline. CG0070 will be administered weekly x 6 on Weeks 1, 2, 3, 4, 5, and 6. If the patient has persistent high-grade disease at Week 13, the patient will receive another cycle of 6 weekly treatments. If there is no disease present at Week 13 (e.g. complete response) then the patient will receive 3 weekly treatments. Beginning at Week 25, patients will receive weekly x 3 treatments every 12 weeks through week 49then every 24 weeks thereafter. | Biological: CG0070<br>* Engineered Oncolytic Adenovirus<br>Other: n-dodecyl-B-D-maltoside<br>* Transduction-enhancing agent.<br>* Other names: DDM;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate in patients with carcinoma in situ (with or without concomitant high-grade Ta or T1 papillary disease) | Percentage of patients with a complete response as defined by FDA guidance document dated February 2018 for NMIBC. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Duration of response (DOR) | Median duration of response in patients with a CR or PR in subjects | 24 months | 
| Median progression free survival | Median duration of progression free survival of subjects | 24 months | 
| Time to tumor progression (TTP) | Median time until patient disease progression (PD) in subjects | 24 months | 
| Incidence of adverse events when CG0070 administered alone. | Percentage of patients with adverse events by grade as determined by NCI CTCAE v5.0. | 24 months | 
| Comparison of complete response in patients with persistent disease versus relapsed disease at baseline. | Percentage in CR | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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high-grade Ta papillary disease, high-grade T1 papillary disease, carcinoma in situ, Bacillus-Calmette-Guerin unresponsive