Phase 1 Study Of Multi-Dose Administration Of Intravesical CG0070 In Patients With Non-Muscle Invasive Bladder Cancer (NMIBC)

Main Category: Urology / Nephrology
Also Included In: Cancer / Oncology;  Clinical Trials / Drug Trials
Article Date: 28 Jun 2008 - 1:00 PDT

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ORLANDO, FL (UroToday.com) - CG0070 is a replication-competent adenovirus modified to replicate preferentially in retinoblastoma pathway-defective cancers and to express granulocyte-macrophage colony-stimulating factor (GM-CSF). This study initially assessed escalating single dose intravesical (IV) administration of CG0070, and reported a tolerable safety profile with signs of anti-tumor activity. The study was amended to evaluate the safety and feasibility of repeat administration of CG0070 in patients with NMIBC after failing BCG treatment.

Patients with recurrent CIS, Ta, or T1 disease were eligible to receive repeat administration of CG0070 at doses of 1x1012, 3x1012, 1x1013, or 3x1013 viral particles (vp) at one of two schedules: six administrations given once weekly or three administrations given once every 4 weeks. Patients are assessed for adverse events, induction of urine and plasma cytokines, CG0070 pharmacokinetics in urine and plasma, and tumor response.

22 patients have been treated. No serious adverse events have been reported in either the single dose or multi-dose administrations. In the multi-dose schedules at dose level 1, common related, adverse events include bladder discomfort/spasm, hematuria, dysuria, fatigue, tissue excretion, urgency, and frequency (all grade 1/2). There has been one episode of grade 3 transient lymphopenia in a patient receiving multidose CG0070 after the third dose and no grade 4 toxicities noted. After the initial instillation there was a significant increase in GM-CSF in the urine, but this was significantly blunted in subsequent instillations. Most patients responded to the agent.

The authors concluded that single dose IV administration of CG0070 is well tolerated at doses up to 3 x 1013 vp with limited local and systemic toxicity. Multi-dose administration of IVe CG0070 at 1x1012 vp given weekly has a tolerable side effect profile, but there appears to be an immune response against the agent that prevents expression of GM-CSF and may well prevent anti-tumor activity.

Presented by James M McKiernan, MD, Donald L Lamm, MD, Maxwell V Meng, MD, John J Nemunaitis, MD, James C Arseneau, MD, Joe Stephenson, MD, James M Burke, MD, Junko Aimi, MD, Daniel J Maslyar, MD, at the Annual Meeting of the American Urological Association (AUA) - May 17 - 22, 2008. Orange County Convention Center - Orlando, Florida, USA.

Reported by UroToday.com Contributing Editor David P. Wood, MD

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