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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Escalation: Assigned dose level (mg/m2), IV over 120 minutes, Days 1 and 3 Cohort A: 500 mg/m2, IV over 120 minutes, Days 1 and 3 Cohort B: MTD mg/m2, IV over 240 minutes, Days 1 and 3
Oxaliplatin- 85 mg/m2, IV over 120 minutes, day 1 Leucovorin/folinic acid- 400 mg/m2, IV over 90 minutes, day 1 Irinotecan- 150 mg/m2, IV over 90 minutes, day 1 5FU- 2400 mg/m2, IV over 42-48 hours after irinotecan, day 1
Rogel Cancer Center
Ann Arbor, Michigan, United States
Number of subjects with dose-limiting toxicity during the first 15 days of devimistat in combination with modified FOLFIRINOX in the dose escalation cohort
The maximum tolerated dose (MTD) will be determined based on dose limiting toxicity
Time frame: 15 days post the start of combination therapy
Median Progression Free Survival (PFS) of devimistat plus modified FOLFIRINOX across all cohorts
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.
Time frame: up to 42 months after enrollment
Number of subjects with reported adverse events and reportable serious events
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).
Time frame: up to 25 months after enrollment
Overall Response Rate (ORR) of devimistat plus modified FOLFIRINOX
ORR will be determined as per the RECISTv1.1 criteria
Time frame: up to 42 months after enrollment
Overall Survival (OS) of devimistat plus modified FOLFIRINOX
OS will be defined from the date of initial treatment to either date of death or censoring.
Time frame: up to 42 months after enrollment
Overall Survival (OS) of devimistat plus modified FOLFIRINOX based on gender
OS will be defined from the date of initial treatment to either date of death or censoring.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: up to 42 months after enrollment
Duration of response (DoR) of devimistat plus modified FOLFIRINOX
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.
Time frame: up to 42 months after enrollment
To assess pharmacokinetics (Cmax) of devimistat
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)
Time frame: up to 42 months after enrollment
To assess pharmacokinetics (AUCinf) of devimistat
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)
Time frame: up to 42 months after enrollment
To assess pharmacokinetics (t1/2) of devimistat
The PK parameters of devimistat (and its metabolites, if appropriate), including but not limited to elimination half-life (t1/2)
Time frame: up to 42 months after enrollment
To assess pharmacokinetics (tmax) of devimistat
The PK parameters of devimistat (and its metabolites, if appropriate), including but not limited to time to reach the maximum plasma concentration (tmax)
Time frame: up to 42 months after enrollment
To assess pharmacokinetics (CL) of devimistat
The PK parameters of devimistat (and its metabolites, if appropriate), including but not limited to clearance (CL)
Time frame: up to 42 months after enrollment
To assess pharmacokinetics (Vd) of devimistat
The PK parameters of devimistat (and its metabolites, if appropriate), including but not limited to volume of distribution (Vd)
Time frame: up to 42 months after enrollment
To determine the median Progression Free Survival (PFS) of devimistat plus modified FOLFIRINOX based on gender
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.
Time frame: up to 42 months after enrollment