NCT01438112

Efficacy Study of Recombinant Adenovirus for Non Muscle Invasive Bladder Cancer

An Integrated Phase II/III, Open Label, Randomized and Controlled Study of the Safety and Efficacy of CG0070 Adenovirus Vector Expressing GM-CSF in Patients With NMIBC With Carcinoma In Situ Disease Who Have Failed BCG

• Status: Terminated
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 22 (actual)
• Sponsor: CG Oncology, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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 uniform distribution of viral particles and exposure to the tumor during those 30-60 minutes instillations as contrast to the intra-tumor injection, intra-arterial or intravenous injection of viral particles in other oncolytic viral trials. Some or most of these delivering methodologies have obvious intrinsic imperfections and potential toxicity. This unique opportunity of an relatively easy intravesical tumor exposure is difficult to duplicate in other solid tumor models. The replication of CG0070 in the majority of patients during the first phase I/II trial indicated tumor lysis with release of tumor specific or tumor associated antigens that have been stably expressed, in abundant quantities during tumor cell death. Release of tumor antigens have been the key elements, together with sufficient on-site GM-CSF, in stimulating strong cross-presentation and confirmation signals to the antigen presenting cells such as dendritic cells interacting with CD4+ and CD8+ T cells. This concept of a "real time" vaccine like regimen is expected to compare favorably with other forms of cancer immunotherapy treatment such as BCG in this patient population. It is with this thought that CG0070 may find a success in this setting because of a reasonably and proven complete response rate in residual and failed BCG bladder cancer patients in the first phase I/II study (some cases with only one instillation). Of importance as well, is the demonstration in the study data of a strong GM-CSF expression during its replication phase. Those patients with carcinoma in situ disease and those with RB pathway dysfunction were particularly responsive. It is therefore, desirable to formulate a protocol to encompass the specialty of this oncolytic vaccine and the unique intravesical delivery to prove the efficacy by a randomized controlled study. This opportunity allows a study on the CG0070's beneficial effects, if any, on the standard of care for carcinoma in situ non muscle invasive bladder cancer patients after they failed BCG therapy. The prognosis of this group presently depends mainly on early radical cystectomy, which carries a high morbidity and decrease of quality of life generally viewed as unacceptable for this group of older patients.

Conditions

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

Interventions

Type	Name	Description
BIOLOGICAL	CG0070 Adenovirus Vector	CG0070 adenoviral vector with GM-CSF expression given intravesically 1x10e12 viral particles for each instillations, weekly times six
OTHER	Control Arm: Quadruple Choice	Quadruple Choice Treatment Options: (same as listed above)

Timeline

• Start date: 2014-03-01
• Primary completion: 2016-06-01
• Completion: 2016-06-01
• First posted: 2011-09-21
• Last updated: 2021-04-14

Locations

7 sites across 1 country: United States