Efficacy Study of Recombinant Adenovirus for Non Muscle Invasive Bladder Cancer

NCT01438112 | Terminated Phase 2 DMC

• 1 other identifier: 12154
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 7

Brief Summary

The use of a designed viral vector that can destroy cancer cells while leaving normal cells largely unharmed. The virus also stimulates an immunological response by producing a special factor (GM-CSF) to attract and promote the development of dendritic and T effector cells. It forms the hypothesis that this regimen may be used for people who have failed current forms of treatment and are recommended for cystectomy. It is with hope that this novel therapy will be able to delay or potentially avoid cystectomy for this patient population. Bladder instillation of this agent causes little long lasting side effects and may drastically improve the stimulation of the immune system for local cancer cell death as well as destroying those tumor cells that may have travelled to regional lymph nodes or distant organs.

Conditions

Transitional Cell Carcinoma; Bladder Cancer; Carcinoma in Situ; Carcinoma in Situ Concurrent With Papillary Tumors

Keywords

cancer; bladder cancer; transitional cell; virus; oncolytic; GM-CSF; adenovirus; intravesical; neoadjuvant; cystectomy; gene therapy; oncolytic virus; carcinoma in situ; carcinoma in situ concurrent with papillary tumors

Outcome Measures

Primary Outcomes (2)

• Complete Response Proportion (CR)

  'CR' Proportion is confirmed by negative biopsy, cystoscopy, cytology weekly times 2 with the first assessment three months after first intravesical treatment and then assessed again at 9 month. Two consecutive positive urine cytologies to confirm a persistent or recurrent disease if visual and biopsy is negative. Random biopsy mandatory at the first assessment in the trigone, bladder dome, right, left , anterior and posterior of the bladder wall.

  9 months (Phase II)

• Durable Complete Response Proportion (DCR)

  DCR proportion of DCR lasting 12 months or longer will be conducted after a follow up period of 15 months for each patient. The first complete response assessment will be at 3 month.

  15 months (Phase III)

Secondary Outcomes (4)

• Progression rate to muscle invasive disease

  Throughout the study with expected average of 12 months

• Complete Response Survival

  15 months

• Safety Events

  Expected average of two years throughout the study

• Cystectomy Free Survival

  15 month

Study Arms (2)

CG0070 oncolytic virus

EXPERIMENTAL

Interventions: CG0070 oncolytic virus intravesical instillations weekly X6 with each instillation lasting 45 minutes after prior transduction agent of DDM intravesically for 15 minutes

Biological: CG0070 Adenovirus Vector

Chemotherapy or Interferon

ACTIVE COMPARATOR

Quadruple Choice as interventions 1. Mitomycin C 2. Interferon 3. Valrubicin 4. Gemcitabine

Other: Control Arm: Quadruple Choice

Interventions

CG0070 Adenovirus Vector BIOLOGICAL

CG0070 adenoviral vector with GM-CSF expression given intravesically 1x10e12 viral particles for each instillations, weekly times six

Also known as: oncolytic virus, CG0070, GM-CSF expression, adenoviral vector

CG0070 oncolytic virus

Control Arm: Quadruple Choice OTHER

Quadruple Choice Treatment Options: (same as listed above)

Also known as: Mitomycin C, Interferon, Valrubicin, Gemcitabine

Chemotherapy or Interferon

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be considered high risk, with pathologically confirmed high grade disease (HG) WHO 2004
• Patients must have pathologically-proven unresectable, primary, secondary or concurrent carcinoma in situ disease, defined by having either Ta and/or T1 with CIS, or CIS
• Patients must have no evidence of muscle invasive disease
• Patient need to sign a specific informed consent acknowledging that a delay of cystectomy may lead to an increase chance of progression and/or metastasis with serious or sometimes fatal consequences.
• Patients must have received at least two or more prior courses of intravesical therapy. BCG must have been one of the prior therapies administered. Patients can have either failed BCG induction therapy within a six month period or have been successfully treated with BCG, but subsequently found to have recurrence. The standard course of intravesical therapy must include six weekly treatments (allowable range of instillations per course is 4-9). The second course of BCG can consist of three weekly treatments
• years of age or older
• Residual disease at accrual
• Pathologically diagnosed transitional cell (urothelial) bladder cancer (further details in 10.) patients where radical cystectomy with curative intent is indicated for superficial bladder cancer that is resistant to treatment.
• Patients must be able to enter into the study within five weeks of their most recent diagnostic procedure, which is usually a diagnostic biopsy, a transurethral resection of bladder tumor (TURBT) procedure or other diagnostic scanning such as CT and PET procedures.
• Histopathologically confirmed, transitional cell (urothelial) carcinoma. Urothelial tumors with mixed histology (but with \<50% variant) are eligible.
• No evidence of urethral or renal pelvis TCC by upper tract radiological imaging (e.g., intravenous pyelogram, CT urogram, or retrograde pyelogram) within the past 2 years.
• Eastern Cooperative Oncology Group (ECOG) performance status \<2.
• Not pregnant or lactating
• Patients with child bearing potential must agree to use adequate contraception
• Agree to study specific informed consent and HIPAA authorization for release of personal health information

You may not qualify if:

• Previous systemic chemotherapy or radiation for bladder cancer. Note: Prior immunotherapy or intravesical (administered within the bladder) chemotherapy for superficial disease is acceptable
• No bladder cancer residual disease, such as patients that are rendered disease free by TURBT
• History of anaphylactic reaction following exposure to humanized or human therapeutic monoclonal antibodies, hypersensitivity to GM-CSF or yeast derived products, clinically meaningful allergic reactions or any known hypersensitivity or prior reaction to any of the formulation excipients in the study drugs.
• Known infection with HIV, HBV or HCV.
• Anticipated use of chemotherapy, radiotherapy, or other immunotherapy not specified in the study protocol while on study
• Any underlying medical condition that, in the Investigator's opinion, will make the administration of study vaccine hazardous to the patient, would obscure the interpretation of adverse events, or surgical resection. Anticipated use of chemotherapy, radiotherapy, or other immunotherapy not specified in the study protocol while on study
• Systemic treatment on any investigational clinical trial within 28 days prior to registration.
• Concurrent treatment with immunosuppressive or immunomodulatory agents, including any systemic steroid (exception: inhaled or topically applied steroids, and acute and chronic standard dose NSAIDs, are permitted). Use of a short course (i.e., ≤ 1 day) of a glucocorticoid is acceptable to prevent a reaction to the IV contrast used for CT scans.
• Immunosuppressive therapy, including: cyclosporine, antithymocyte globulin, or tacrolimus within 3 months of study entry.
• History of prior experimental cancer vaccine treatment (e.g., dendritic cell therapy, heat shock vaccine)
• History of partial cystectomy in the setting of bladder cancer primary tumor.
• History of anaphylactic reaction following exposure to humanized or human therapeutic monoclonal antibodies, hypersensitivity to GM-CSF or yeast derived products, clinically meaningful allergic reactions or any known hypersensitivity or prior reaction to any of the formulation excipients in the study drugs.
• History of stage III or greater cancer, excluding urothelial cancer. Basal or squamous cell skin cancers must have been adequately treated and the subject must be disease-free at the time of registration. Subjects with a history of stage I or II cancer, must have been adequately treated and have been disease-free for ≥ 3 years at the time of registration.
• Concomitant active autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, autoimmune thyroid disease, uveitis)
• Progressive viral or bacterial infection

Sponsors & Collaborators

• CG Oncology, Inc.: lead

Study Sites (7)

BCG Oncology

Phoenix, Arizona, 85032-2129, United States

Location

University of California, San Diego- Moores Cancer Center

La Jolla, California, 92093, United States

Location

UCLA Institute of Urological Oncology

Los Angeles, California, 90024, United States

Location

University of California, Davis- Cancer Center

Sacramento, California, 95817, United States

Location

University of Chicago, Department of Surgery, Section of Urology

Chicago, Illinois, 60637, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Vanderbilt University Medical Center Department of Urologic Surgery

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Carcinoma in Situ; Neoplasms; Virus Diseases; Adenoviridae Infections

Interventions

Oncolytic Virotherapy; Mitomycin; Interferons; valrubicin; Gemcitabine

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Infections; DNA Virus Infections

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines

Study Officials

• Alex W Yeung, MBBS

  CG Oncology, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2011
• First Posted: September 21, 2011
• Study Start: March 1, 2014
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: April 14, 2021

Record last verified: 2021-04

Locations

US (7)