Safety, Immunogenicity and Pharmacokinetics of SYN004 in Patients With Solid Tumors (SYN004_Ph_1)
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|ClinicalTrials.gov Identifier: NCT02391727|
Recruitment Status : Completed
First Posted : March 18, 2015
Last Update Posted : November 16, 2018
|Condition or disease||Intervention/treatment||Phase|
|Colon Cancer, Breast Cancer, Cancer of the Head and Neck||Biological: SYN004||Phase 1|
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 mg/m2; Weekly Dose: 62.5 mg/m2. Group 2: Loading dose: 200 mg/m2; Weekly Dose: 125 mg/m2. Group 3: Loading dose: 400 mg/m2; Weekly Dose: 250 mg/m2.
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 Subjects with DLTs will be withdrawn from treatment.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DLTs, or one subject in a dose group experiences a Grade ≥3 infusion reaction, all subjects in that dose group will be withdrawn from treatment.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 1.1) 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 1.1 (i.e., findings of complete or partial response per RECIST 1.1) and meet the other eligibility criteria will be offered up to 3 additional treatment cycles (i.e., 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 3+3 study design.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||May 2015|
|Actual Primary Completion Date :||October 2018|
|Actual Study Completion Date :||October 2018|
open label study
subjects who have received effective treatment for their cancers are eligible
- Number of patients with adverse events [ Time Frame: 28 days of last SYN004 Administration ]cutaneous toxicity, hypersensitivity
- maximum plasma concentration (Cmax) [ Time Frame: 84 days ]Cmax will be determined using noncompartmental methods for SYN004
- time to Cmax (Tmax) [ Time Frame: 84 days ]Tmax will be determined using noncompartmental methods for SYN004
- elimination rate constant (λz) [ Time Frame: 84 days ]λz will be determined using noncompartmental methods for SYN004
- elimination half-life (t½) [ Time Frame: 84 days ]t½ will be determined using noncompartmental methods for SYN004
- mean residence time (MRT) [ Time Frame: 84 days ]MRT will be determined using noncompartmental methods for SYN004
- area under the plasma concentration vs. time curve from 0 (initiation of infusion) to the time of the last detectable concentration (AUC0-t), AUC from time 0 extrapolated to infinity (AUC0-∞) [ Time Frame: 84 days ]AUC0-t and AUC0-∞ will be determined using noncompartmental methods for SYN004
- systemic clearance (CL) [ Time Frame: 84 days ]CL will be determined using noncompartmental methods for SYN004
- volume of distribution in the terminal phase (Vdβ), and estimated steady-state volume of distribution (VSS) [ Time Frame: 84 days ]Vdβ and VSS will be determined using noncompartmental methods for SYN004
- anti-cancer activity [ Time Frame: 84 days ]Measurement of objective response (OR), durability of objective response (DOR), and progression-free survival (PFS). The number and proportion of subjects who achieve objective tumor response (complete response [CR], partial response [PR], and CR+PR) or stable disease (SD) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, according to local radiological assessments from date of first administration of the investigational product to the end of the study treatment.
- To assess biomarkers of relevance to SYN004 mechanism of action and activity [ Time Frame: 84 days ]Blood samples will be collected for the evaluation of IgE antibodies to Galα1,3Gal
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02391727
|United States, Louisiana|
|Ochsner Medical Center|
|New Orleans, Louisiana, United States, 70121|
|United States, Missouri|
|Washington University Medical Center|
|Saint Louis, Missouri, United States, 63110|
|Study Director:||John McClain, MD||Synermore Biologics Co., Ltd.|