Trial of Devimistat in Combination With Modified FOLFIRINOX in Patients With Metastatic Adenocarcinoma of the Pancreas

Phase 1

Withdrawn

• Conditions: Metastatic Pancreatic Adenocarcinoma
• Interventions: Drug: Devimistat; Drug: Modified FOLFIRINOX

• Registration Number: NCT05926206
• Lead Sponsor: University of Michigan Rogel Cancer Center

Brief Summary

This protocol will enroll patients with metastatic pancreatic cancer to receive modified FOLFIRINOX plus devimistat. Patients will be enrolled with 1:1 randomization between Dose Escalation Cohort and Cohort A until required 20 patients have been enrolled on Cohort A following which randomization will end and patients will be enrolled without randomization to Dose Escalation Cohort and then subsequently to Cohort B.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-05-23
• Study First Submitted QC: 2023-06-26
• Status Verified: 2023-07
• Study Start: 2023-07
• Study First Posted: 2023-07-03
• Last Update Submitted: 2023-07-31
• Last Update Posted: 2023-08-02
• Primary Completion: 2027-01
• Study Completion: 2027-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TiTE-CRM Dose Escalation	Modified FOLFIRINOX	Devimistat at Dose Level IV 2 hrs + modified FOLFIRINOX
Expansion Cohort A	Modified FOLFIRINOX	Devimistat 500 mg/m2 IV 2 hrs + modified FOLFIRINOX
Expansion Cohort B	Modified FOLFIRINOX	Devimistat at MTD IV 4 hrs + modified FOLFIRINOX
TiTE-CRM Dose Escalation	Devimistat	Devimistat at Dose Level IV 2 hrs + modified FOLFIRINOX
Expansion Cohort A	Devimistat	Devimistat 500 mg/m2 IV 2 hrs + modified FOLFIRINOX
Expansion Cohort B	Devimistat	Devimistat at MTD IV 4 hrs + modified FOLFIRINOX

Primary Outcome Measures

Name	Time	Method
Number of subjects with dose-limiting toxicity during the first 15 days of devimistat in combination with modified FOLFIRINOX in the dose escalation cohort	15 days post the start of combination therapy	The maximum tolerated dose (MTD) will be determined based on dose limiting toxicity
Median Progression Free Survival (PFS) of devimistat plus modified FOLFIRINOX across all cohorts	up to 42 months after enrollment	The PFS will be defined as time from date of initial treatment to date of radiological or clinical progression (leading to withdrawal from the study treatment), or death from any cause on study treatment, whichever comes first. Follow-up time will be censored at the date of last disease evaluation.

Secondary Outcome Measures

Name	Time	Method
Number of subjects with reported adverse events and reportable serious events	up to 25 months after enrollment	To assess the safety and toxicity of the drug combination by reported adverse events and reportable serious events are defined by the study protocol (NCI Common Toxicity Criteria for Adverse Events (CTCAE) v5.0).
Overall Survival (OS) of devimistat plus modified FOLFIRINOX	up to 42 months after enrollment	OS will be defined from the date of initial treatment to either date of death or censoring.
Overall Response Rate (ORR) of devimistat plus modified FOLFIRINOX	up to 42 months after enrollment	ORR will be determined as per the RECISTv1.1 criteria
Overall Survival (OS) of devimistat plus modified FOLFIRINOX based on gender	up to 42 months after enrollment	OS will be defined from the date of initial treatment to either date of death or censoring.
Duration of response (DoR) of devimistat plus modified FOLFIRINOX	up to 42 months after enrollment	DoR will be measured from the start date of the best response achieved until the date of relapse (i.e., progression). Continuing responders will be right-censored as of the most recent date on which their response status had been assessed. DoR applies to only the patients who achieve either a complete response or a partial response.
To assess pharmacokinetics (Cmax) of devimistat	up to 42 months after enrollment	The PK parameters of devimistat (and its metabolites, if appropriate), including but not limited to peak plasma concentration (Cmax) versus time curve from time 0 to t (AUC0-t)
To assess pharmacokinetics (Vd) of devimistat	up to 42 months after enrollment	The PK parameters of devimistat (and its metabolites, if appropriate), including but not limited to volume of distribution (Vd)
To determine the median Progression Free Survival (PFS) of devimistat plus modified FOLFIRINOX based on gender	up to 42 months after enrollment	The PFS will be defined as time from date of initial treatment to date of radiological or clinical progression (leading to withdrawal from the study treatment), or death from any cause on study treatment, whichever comes first. Follow-up time will be censored at the date of last disease evaluation.
To assess pharmacokinetics (AUCinf) of devimistat	up to 42 months after enrollment	The PK parameters of devimistat (and its metabolites, if appropriate), including but not limited to area under the concentration versus time curve from time 0 to infinity (AUCinf)
To assess pharmacokinetics (t1/2) of devimistat	up to 42 months after enrollment	The PK parameters of devimistat (and its metabolites, if appropriate), including but not limited to elimination half-life (t1/2)
To assess pharmacokinetics (tmax) of devimistat	up to 42 months after enrollment	The PK parameters of devimistat (and its metabolites, if appropriate), including but not limited to time to reach the maximum plasma concentration (tmax)
To assess pharmacokinetics (CL) of devimistat	up to 42 months after enrollment	The PK parameters of devimistat (and its metabolites, if appropriate), including but not limited to clearance (CL)

Trial Locations

Locations (1)

Rogel Cancer Center; 🇺🇸 Ann Arbor, Michigan, United States