Ignite Creation Date:
2024-05-06 @ 3:59 PM
Last Modification Date:
2024-10-26 @ 2:01 PM
Study NCT ID:
NCT04834778
Status:
COMPLETED
Last Update Posted:
2024-03-08
First Post:
2021-04-02
Brief Title:
A Study of HC-5404-FU to Establish the Maximum Tolerated Dose MTD
Sponsor:
HiberCell Inc
Organization:
HiberCell Inc
Study Overview
Official Title:
A Multicenter Open-label Phase 1a Study of HC-5404-FU in Subjects With Advanced Solid Tumors
Status:
COMPLETED
Status Verified Date:
2024-03
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:
None
Brief Summary:
Study HC-404-FCP-2011 is a first in human Phase 1a multi-center open-label study to establish the maximum tolerated dose MTD and evaluate the safety and tolerability of oral dosing of HC-5404-FU in a dose-escalating fashion Up to 36 qualified subjects at 3 to 5 US sites who have specific tumor types of renal cell carcinoma RCC gastric cancer GC metastatic breast cancer MBC small cell lung cancer SCLC and other solid tumors eg non-small cell lung cancer colorectal cancer carcinoma of unknown primary with the exception of rapidly progressing neoplasms eg pancreatic cancer glioblastoma hepatocellular carcinoma will receive HC-5404-FU Every effort will be made to ensure approximately 50 of all subjects enrolled will be subjects with RCC and GC The starting dose level is 25 mg twice daily BID escalating to 50 100 and 200 mg BID as safety allows following the Bayesian Optimal Interval BOIN design The safety monitoring committee SMC will evaluate the DLTs and cumulative safety and PK data at the end of each cohort Based on the SMC recommendations after a comprehensive review of PK and safety data for 200 mg BID dose higher dose levels will be evaluated starting with 400 mg BID The dose will escalate to 600 mg and then 900 mg following the BOIN design starting with 1 subject at each escalated dose until the MTD is reached or the sponsor or SMC declares the dose most appropriate for clinical development This Phase 1a will be expanded into a Phase 1b2a study through a protocol amendment and will then assess the dose and tumor types selected in Phase 1a as the most appropriate for further clinical development Subjects will be dosed until unacceptable toxicity disease progression per immune-related Response Evaluation Criteria in Solid Tumors iRECIST subject withdrawal any other administrative reasons or after 2 years of treatment whichever occurs first Efficacy will be assessed via Response Evaluation Criteria in Solid Tumors 11 RECIST 11 computed tomography CT scans will be conducted every 6 weeks Safety including occurrence of dose-limiting toxicities DLTs pharmacokinetics PK and biomarker parameters will also be assessed
Detailed Description:
HC 5404-FU will be orally administered BID with food or within 30 minutes of completing a meal starting at 25 mg with doses escalating to 50 100 200 400 600 and 900 mg BID as safety allows Up to 24 subjects will be enrolled to ensure 12 subjects complete the study at the estimated MTD of HC 5404-FU Dosing will occur in 3-week cycles Subjects are to spend Cycle 1Day 1 C1D1 in the clinic followed by an overnight stay for safety monitoring and PK sampling Subjects will be hospitalized for administration of first 3 doses C1D1 am and pm doses and Cycle 1Day 2 C1D2 am dose on Days 8 15 and 21 the am dose will be taken in the clinic after the planned PK samples All other doses are to be self administered at home After the initial hospital stay at the start of study subjects will be seen in outpatient clinic on Days 8 15 and 21 of Cycle 1 for PK assessment and thereafter the first day of each cycle for physical and laboratory assessments adverse event AE and dosing compliance monitoring the end of treatment visit will also be in person in outpatient clinic
Following completion of the treatment period of the study subjects will be monitored for survival up for up to 24 months after the last post treatment follow-up visit
Dose escalation will follow the Bayesian Optimal Interval BOIN design The decision to escalate to the next dose level will be based on safety assessments after all subjects of a cohort have reached the end of Cycle 1Day 21 DLT evaluation period The safety monitoring committee SMC will be responsible for dose escalation decisions including whether to modify the dose escalation based on the DLT observations and review of available PK data
The target toxicity rate of 30 with limits of 0236 to 0359 for escalationde escalation will be employed to determine the MTD With these predefined parameters when the observed toxicity rate in a dose level is less than 0236 the dose for the next cohort can escalate If the observed toxicity rate is higher than 0359 the dose will de escalate Otherwise the dose remains the same
Individual subjects may be considered for treatment at a higher dose than the dose to which they were initially assigned after subject has completed 2 cycles of treatment and 1 postbaseline CT scan and maintained at least a stable disease SD response In order to escalate a dose level the subject must have tolerated hisher current dose level without experiencing a DLT and the dose level to which the subject is planned to be escalated must have completed a DLT evaluation period not exceeded the MTD and been declared safe Each subject can go through 2 dose escalations and do not need to go through a DLT evaluation period for either escalation Intrasubject dose escalation will be considered on a case-by-case basis each case to be assessed and approved by the sponsor
Following completion of the treatment period of the study subjects will be monitored for survival up for up to 24 months after the last post treatment follow-up visit
Dose escalation will follow the Bayesian Optimal Interval BOIN design The decision to escalate to the next dose level will be based on safety assessments after all subjects of a cohort have reached the end of Cycle 1Day 21 DLT evaluation period The safety monitoring committee SMC will be responsible for dose escalation decisions including whether to modify the dose escalation based on the DLT observations and review of available PK data
The target toxicity rate of 30 with limits of 0236 to 0359 for escalationde escalation will be employed to determine the MTD With these predefined parameters when the observed toxicity rate in a dose level is less than 0236 the dose for the next cohort can escalate If the observed toxicity rate is higher than 0359 the dose will de escalate Otherwise the dose remains the same
Individual subjects may be considered for treatment at a higher dose than the dose to which they were initially assigned after subject has completed 2 cycles of treatment and 1 postbaseline CT scan and maintained at least a stable disease SD response In order to escalate a dose level the subject must have tolerated hisher current dose level without experiencing a DLT and the dose level to which the subject is planned to be escalated must have completed a DLT evaluation period not exceeded the MTD and been declared safe Each subject can go through 2 dose escalations and do not need to go through a DLT evaluation period for either escalation Intrasubject dose escalation will be considered on a case-by-case basis each case to be assessed and approved by the sponsor
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None