Ignite Creation Date:
2024-05-05 @ 5:20 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00437736
Status:
COMPLETED
Last Update Posted:
2015-09-17
First Post:
2007-02-20
Brief Title:
A Phase I Dose Finding Study of APO010 in Patients With Solid Tumors
Sponsor:
Valerio Therapeutics
Organization:
Valerio Therapeutics
Study Overview
Official Title:
Phase I Dose Finding and Pharmacokinetic Study of Intravenous APO010 a Recombinant Form of Human Fas Ligand in Patients With Solid Tumors
Status:
COMPLETED
Status Verified Date:
2015-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
AP1001
Brief Summary:
Two-centre open label uncontrolled dose-finding phase I study to determine the safety and tolerability of APO010 administered by intravenous bolus injection once per week It will be the first time this agent will be administered to humans At lower dose levels the first cycle duration is 7 weeks In subsequent cycles APO010 is administered as 4 weekly doses followed by a two-week drug rest cycle duration is 6 weeks Based on preclinical studies of APO010 may cause liver toxicity and a drop in platelets that recover within 5 days The main aim of the study is to identify the recommended dose of APO010 for future clinical studies of APO010
Detailed Description:
Two-centre open label uncontrolled dose-finding phase I study to determine the safety and tolerability of APO010 administered by intravenous bolus injection once per week in patients with solid tumors for whom therapy of proven efficacy does not exist or is no longer effective The dose-escalations will follow a classical Fibonacci schedule meaning at least three patient per dose-level prior to further escalation The dose-level assignment and patient registration is centralized by SENDO-Switzerland Milan offices
APO010 Apoxis proprietary humanized recombinant mega-Fas-ligand is a novel First in class investigational anticancer agent APO010 is a protein that by specific binding to its cognate Fas receptor on the cell surface induces apoptosis programmed cell death This is called the extrinsic apoptotic pathway of cells APO010 has shown to exert anticancer activity in vitro and in animal models carrying a human xenograft of a variety of cancers including malignancies such as multiple myeloma non-small cell lung cancer NSCLC ovarian cancer Its activity is cell cycle independent it does not cross react with known multi-drug resistance mechanism MDR and appears to be synergistic with a variety of commonly used anticancer drugs Hence APO010 may an attractive candidate for combination anticancer therapy and may be a effective drug in overcoming MDR
In this study the starting dose is 25 microgramm2 Normally 16 of the No-observed-adverse-effect level NOAEL dose-level in monkeys would be chosen as the first dose-level however it has been decided to start at 25 of that dose-level Across species mice rats and Cynomolgus monkeys the rise in transaminases and drop in platelets occurred at 30 microgramm2 The Nadir of these toxicities occurred within 6 hours and full recovery at day 5 after the bolus injection
At the first occurrence of non-reversible within 1 week Common Toxicity Criteria CTC v30 Grade 2 liver function toxicity Aspartate transaminase ASTAlanine transaminase ALT or alkaline phosphatase ie Dose Limiting Toxicity DLT the patient accrual will be placed on hold until recovery and the subsequent timing of patient accrual to the existing and subsequent cohorts will be re-defined by the sponsor the principal investigators and SENDO
Pharmacokinetic assessments will be carried out in all patients during the first and in consenting patients during the second cycles of treatment
Assessment for immunogenicity binding andor neutralizing antibodies against APO010 will be carried out in all patients in all cycles of treatment before each dose and 2 weeks after the final dose
APO010 Apoxis proprietary humanized recombinant mega-Fas-ligand is a novel First in class investigational anticancer agent APO010 is a protein that by specific binding to its cognate Fas receptor on the cell surface induces apoptosis programmed cell death This is called the extrinsic apoptotic pathway of cells APO010 has shown to exert anticancer activity in vitro and in animal models carrying a human xenograft of a variety of cancers including malignancies such as multiple myeloma non-small cell lung cancer NSCLC ovarian cancer Its activity is cell cycle independent it does not cross react with known multi-drug resistance mechanism MDR and appears to be synergistic with a variety of commonly used anticancer drugs Hence APO010 may an attractive candidate for combination anticancer therapy and may be a effective drug in overcoming MDR
In this study the starting dose is 25 microgramm2 Normally 16 of the No-observed-adverse-effect level NOAEL dose-level in monkeys would be chosen as the first dose-level however it has been decided to start at 25 of that dose-level Across species mice rats and Cynomolgus monkeys the rise in transaminases and drop in platelets occurred at 30 microgramm2 The Nadir of these toxicities occurred within 6 hours and full recovery at day 5 after the bolus injection
At the first occurrence of non-reversible within 1 week Common Toxicity Criteria CTC v30 Grade 2 liver function toxicity Aspartate transaminase ASTAlanine transaminase ALT or alkaline phosphatase ie Dose Limiting Toxicity DLT the patient accrual will be placed on hold until recovery and the subsequent timing of patient accrual to the existing and subsequent cohorts will be re-defined by the sponsor the principal investigators and SENDO
Pharmacokinetic assessments will be carried out in all patients during the first and in consenting patients during the second cycles of treatment
Assessment for immunogenicity binding andor neutralizing antibodies against APO010 will be carried out in all patients in all cycles of treatment before each dose and 2 weeks after the final dose
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| S065APO01 | None | None | None |