Ignite Creation Date:
2024-05-06 @ 3:52 AM
Last Modification Date:
2024-10-26 @ 11:40 AM
Study NCT ID:
NCT02391727
Status:
COMPLETED
Last Update Posted:
2018-11-16
First Post:
2015-03-09
Brief Title:
Safety Immunogenicity and Pharmacokinetics of SYN004 in Patients With Solid Tumors
Sponsor:
Synermore Biologics Co Ltd
Organization:
Synermore Biologics Co Ltd
Study Overview
Official Title:
A Phase 1 Multi-center Open-Label Dose Escalation Study of SYN004 in Patients With Solid Tumors to Evaluate the Safety Immunogenicity and Pharmacokinetics of SYN004 Following Administration of Eight Intravenous Doses
Status:
COMPLETED
Status Verified Date:
2018-11
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:
SYN004_Ph_1
Brief Summary:
A first-in-human evaluation of SYN004 a monoclonal antibody that binds to the EGF receptor on cancer cells Cetuximab a marketed antibody has been shown to be effective by inhibiting the growth of cancer cells thereby prolonging the life of patients who have received it SYN004 is a closely related monoclonal antibody also binds to the EGF receptor in the same way SYN004 might also inhibit cancer cells and prolong life but has been engineered to avoid some of the hypersensitivity reactions known to provoked by cetuximab
Detailed Description:
Study Design
In this open-label dose escalation study subjects will receive a single IV loading dose of SYN004 on Day 1 of the first treatment week followed by up to 7 fixed weekly doses of SYN004 Subjects will be assigned to loading and fixed doses by dose group
Each dose group will comprise 3 subjects and may be expanded to 6 subjects Subjects will enter dose groups in the order in which they are enrolled There will be no intra-subject dose adjustments
Only 1 subject in a cohort may receive the loading dose of SYN004 on any given day at least 1 day must elapse before the next subject in the cohort receives the loading dose
Study SYN004-001 Dose Matrix Three initial subjects will be enrolled followed by an additional three if specified by protocol Dose levels are specified below
Group 1 Loading dose 100 mgm2 Weekly Dose 625 mgm2 Group 2 Loading dose 200 mgm2 Weekly Dose 125 mgm2 Group 3 Loading dose 400 mgm2 Weekly Dose 250 mgm2
After each dose of IV SYN004 subjects will be observed in the clinic for 12 hours After the loading dose subjects will undergo safety evaluations on Days 2 3 and 5 Safety evaluation will also be performed on Day 1 pre-treatment and Day 3 of each fixed dose treatment week
Dose-limiting toxicities DLTs are defined as any Grade 3 AE assessed by the investigator or Medical Monitor with agreement of the Safety Review Board SRB as related to SYN004 Subjects with DLTs will be withdrawn from treatment If 2 or more subjects in a dose group experience DLTs or one subject in a dose group experiences a Grade 3 infusion reaction all subjects in that dose group will be withdrawn from treatment
Subjects in the dose groups are considered evaluable for dose escalation decisions if they receive at least 4 doses of SYN004 or discontinue SYN004 because of a DLT
Subjects who withdraw or are terminated per protocol before receiving 4 doses of SYN004 will be replaced
For subjects who receive at least 4 doses of SYN004 End of Study CT scans for RECIST version 11 evaluation will be performed six 6 days following the final SYN004 treatment
There will be a 28-day safety monitoring period following the final dose of SYN004 for all subjects in the study All subjects will attend an End-of-Study Visit 28 days after the final dose of SYN004
Subjects who complete Cycles 1 and 2 who have evidence of improvement per RECIST 11 ie findings of complete or partial response per RECIST 11 and meet the other eligibility criteria will be offered up to 3 additional treatment cycles ie up to 12 additional weekly doses of SYN004 in the SYN004-001 Extension Study During the Extension Study subjects will receive the same fixed dose of SYN004 they received in Cycles 1 and 2
Dose escalation will proceed according to a standard 33 study design
In this open-label dose escalation study subjects will receive a single IV loading dose of SYN004 on Day 1 of the first treatment week followed by up to 7 fixed weekly doses of SYN004 Subjects will be assigned to loading and fixed doses by dose group
Each dose group will comprise 3 subjects and may be expanded to 6 subjects Subjects will enter dose groups in the order in which they are enrolled There will be no intra-subject dose adjustments
Only 1 subject in a cohort may receive the loading dose of SYN004 on any given day at least 1 day must elapse before the next subject in the cohort receives the loading dose
Study SYN004-001 Dose Matrix Three initial subjects will be enrolled followed by an additional three if specified by protocol Dose levels are specified below
Group 1 Loading dose 100 mgm2 Weekly Dose 625 mgm2 Group 2 Loading dose 200 mgm2 Weekly Dose 125 mgm2 Group 3 Loading dose 400 mgm2 Weekly Dose 250 mgm2
After each dose of IV SYN004 subjects will be observed in the clinic for 12 hours After the loading dose subjects will undergo safety evaluations on Days 2 3 and 5 Safety evaluation will also be performed on Day 1 pre-treatment and Day 3 of each fixed dose treatment week
Dose-limiting toxicities DLTs are defined as any Grade 3 AE assessed by the investigator or Medical Monitor with agreement of the Safety Review Board SRB as related to SYN004 Subjects with DLTs will be withdrawn from treatment If 2 or more subjects in a dose group experience DLTs or one subject in a dose group experiences a Grade 3 infusion reaction all subjects in that dose group will be withdrawn from treatment
Subjects in the dose groups are considered evaluable for dose escalation decisions if they receive at least 4 doses of SYN004 or discontinue SYN004 because of a DLT
Subjects who withdraw or are terminated per protocol before receiving 4 doses of SYN004 will be replaced
For subjects who receive at least 4 doses of SYN004 End of Study CT scans for RECIST version 11 evaluation will be performed six 6 days following the final SYN004 treatment
There will be a 28-day safety monitoring period following the final dose of SYN004 for all subjects in the study All subjects will attend an End-of-Study Visit 28 days after the final dose of SYN004
Subjects who complete Cycles 1 and 2 who have evidence of improvement per RECIST 11 ie findings of complete or partial response per RECIST 11 and meet the other eligibility criteria will be offered up to 3 additional treatment cycles ie up to 12 additional weekly doses of SYN004 in the SYN004-001 Extension Study During the Extension Study subjects will receive the same fixed dose of SYN004 they received in Cycles 1 and 2
Dose escalation will proceed according to a standard 33 study design
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