Efficacy Study of Recombinant Adenovirus for Non Muscle Invasive Bladder Cancer

Launched by CG ONCOLOGY, INC. · Sep 20, 2011

Keywords

ClinConnect Summary

After the phase I/II CG0070 trial review, it became apparent that the use of CG0070 oncolytic vaccine as an intravesical agent for oncolytic lysis of tumor cells, together with the transcription of GM-CSF on site, may have distinct advantages. This first study showed excellent tumor response rates of 48-77% depending on the dose schedule administered. All of these patients had residual non-muscle invasive bladder cancer who have previously failed BCG therapy at the time of treatment.

With the addition of a transduction agent such as DDM, the intravesical instillation of CG0070 enabled unif...

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Eligibility criteria

• Inclusion Criteria:
• • 1. Patients must be considered high risk, with pathologically confirmed high grade disease (HG) WHO 2004
• • 2. 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
• • 3. Patients must have no evidence of muscle invasive disease
• • 4. 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.
• • 5. 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
• • 6. 18 years of age or older
• • 7. Residual disease at accrual
• • 8. 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.
• • 9. 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.
• • 10. Histopathologically confirmed, transitional cell (urothelial) carcinoma. Urothelial tumors with mixed histology (but with \<50% variant) are eligible.
• • 11. 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.
• • 12. Eastern Cooperative Oncology Group (ECOG) performance status \<2.
• • 13. Not pregnant or lactating
• • 14. Patients with child bearing potential must agree to use adequate contraception
• • 15. Agree to study specific informed consent and HIPAA authorization for release of personal health information
• • 16. Adequate baseline CBC, renal and hepatic function. Renal parameters as detailed above. Absolute lymphocyte count ≥ 1,000/μL before all doses of CG0070
• • 17. Patient to provide a tumor specimen for determination of RB pathway status
• Exclusion Criteria:
• • 1. Previous systemic chemotherapy or radiation for bladder cancer. Note: Prior immunotherapy or intravesical (administered within the bladder) chemotherapy for superficial disease is acceptable
• • 2. No bladder cancer residual disease, such as patients that are rendered disease free by TURBT
• • 3. 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.
• • 4. Known infection with HIV, HBV or HCV.
• • 5. Anticipated use of chemotherapy, radiotherapy, or other immunotherapy not specified in the study protocol while on study
• • 6. 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
• • 7. Systemic treatment on any investigational clinical trial within 28 days prior to registration.
• • 8. 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.
• • 9. Immunosuppressive therapy, including: cyclosporine, antithymocyte globulin, or tacrolimus within 3 months of study entry.
• • 10. History of prior experimental cancer vaccine treatment (e.g., dendritic cell therapy, heat shock vaccine)
• • 11. History of partial cystectomy in the setting of bladder cancer primary tumor.
• • 12. 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.
• • 13. 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.
• • 14. Concomitant active autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, autoimmune thyroid disease, uveitis)
• • 15. Progressive viral or bacterial infection
• • 16. All infections must be resolved and the patient must remain afebrile for seven days without antibiotics prior to being placed on study
• • 17. 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 not permit adequate surgical resection.
• • 18. Unwilling or unable to comply with the protocol or cooperate fully with the investigator and site personnel