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 Non-Muscle Invasive Bladder Cancer With Carcinoma In Situ Disease Who Have Failed BCG
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.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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 consectutive 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)
United States: Food and Drug Administration