| General information |
| Database: | DB00567 |
| Objective: | a phase I doseescalation study was performed to determine the maximum tolerated dose (MTD) of the immunotoxin VB4845 in patients with nonmuscleinvasive bladder cancer (NMIBC) refractory to or intolerant of bacillus CalmetteGuerin (BCG). evaluation of the safety, tolerability, pharmacokinetics, immunogenicity, and efficacy of VB4845. |
| Authors: | Kowalski M, et al |
| Title: | a phase I study of an intravesically administered immunotoxin targeting EpCAM for the treatment of nonmuscleinvasive bladder cancer in BCGrefractory and BCGintolerant patients. |
| Journal: | Drug Des Devel Ther. |
| Year: | 2010 |
| PMID: | 21151619 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | VB4845
|
| Target: | Tumorassociated calcium signal transducer 1
|
| Cancer Type: | bladder cancer |
| Cancer Subtype: | EpCAMpositive Grade 2 or 3 nonmuscleinvasive bladder cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | an openlabel, multicenter, doseescalatingtrial |
| Key Patients Feature: | Only patients 18 years of age or older with immunohistochemically confirmed EpCAMpositive Grade 2or 3 NMIBC (Ta, T1, in situ carcinoma [TIS]), eitherrefractory to (recurrence within 2 years following atleast one complete cycle of BCG therapy) or intolerant of BCG therapy, were eligible for this study.Other key inclusion criteria were adequate renal (serum creatinine#1.5 ¡Á the upper limit of normal (ULN) or creatinineclearance $60 mLs/min), hepatic (alanine aminotransferaseand aspartate aminotransferase #2.5 ¡Á ULN and bilirubin levels #1.5 ¡Á ULN), and hematological(granulocytes $1500/¦ÌL, platelets $100, 000/¦ÌL, andhemoglobin .8 g/dL) function. Women of childbearingpotential, and all men, must have agreed to use adequatecontraception prior to and for the duration of the study |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Treatment was administered in ascending dose cohorts ranging from 0.1 to 30.16 mg. After receiving weekly instillations of VB4845 to the bladder via catheter for 6 consecutive weeks, patients were follotheyd for 46 weeks posttherapy and assessed at week 12. |
| Primary End Point: | maximum tolerated dose (MTD) of the immunotoxin VB4845 |
| Secondary End Point: | safety, tolerability, pharmacokinetics, immunogenicity, and efficacy of VB4845 |
| Patients Number: | 64 |
| Trial Results |
| DLT_MTD: | An MTD was not determined, as a doselimiting toxicity was not identified over the doserange tested. VB4845 therapy was safe and well tolerated with most adverse events reported asmild; as a result, no patients were removed from the study in response to toxicity. |
| Objective Response Rate: | A complete response was achieved in 39% of patients at the 12week time point |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common treatmentrelated Aes were dysuria and hematuria. Systemic AEs included fatigue, fever and chills, loss of appetite, myalgia, dizziness, and nausea. The frequency of treatmentrelated AEs did not increase with dose escalation. All treatmentrelated AEs were Grade 1 or 2, with the exception of one Grade 3 occurrence of hematuria that was reported as possibly related to VB4845 administration. |
| Conclusions: | VB4845 dosed on a weekly basis for 6 weeks was very well tolerated at all dose levels. Although an MTD was not determined at the doses administered, VB4845 showed evidence of an antitumor effect that warrants further clinical investigation for the treatment of NMIBC in this patient population. |