Trial of Devimistat in Combination With Modified FOLFIRIN... | NCT05926206

ID	Type	Description	Link
HUM00228911	Other Identifier	University of Michigan

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
TiTE-CRM Dose Escalation	Experimental	Devimistat at Dose Level IV 2 hrs + modified FOLFIRINOX	Drug: Devimistat Drug: Modified FOLFIRINOX
Expansion Cohort A	Experimental	Devimistat 500 mg/m2 IV 2 hrs + modified FOLFIRINOX	Drug: Devimistat Drug: Modified FOLFIRINOX
Expansion Cohort B	Experimental	Devimistat at MTD IV 4 hrs + modified FOLFIRINOX	Drug: Devimistat Drug: Modified FOLFIRINOX

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Devimistat	Drug	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

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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	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.	up to 42 months after enrollment

Secondary Outcomes

Measure	Description	Time Frame
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).	up to 25 months after enrollment

Eligibility Module

Eligibility Criteria

Eligibility Criteria:

Histologically or cytologically confirmed metastatic stage IV adenocarcinoma of the pancreas
No prior systemic treatment for advanced pancreatic adenocarcinoma. Prior adjuvant or neoadjuvant treatment is allowed provided it completed ≥ 6 months prior to disease recurrence. Palliative radiation therapy is allowed provided it completed ≥ 2 weeks prior to starting trial therapy
Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
Age 18 years or greater
Measurable disease determined using guidelines of Response Evaluation Criteria in Solid Tumors (RECIST version 1.1)
Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must agree to use acceptable highly effective contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive(s), intrauterine hormone releasing system (IUS), bilateral tubal occlusion or vasectomized partner) starting at screening, during the study, and for 9 months after last study dose and must have a negative serum or urine pregnancy test during screening.
Males with female partners (of childbearing potential) must agree to use double barrier contraceptive measure (a combination of male condom with either cap, diaphragm or sponge with spermicide) in addition to oral contraception, or avoidance of intercourse during the study and for 6 months after last study dose is received.
At least 4 weeks from major surgery with resolution of any sequela to date of enrollment
Laboratory values ≤2 weeks during screening must be: Platelet count ≥ 100,000 cells/mm3, Absolute neutrophil count ≥ 1500 cells/mm3, Hemoglobin > 9 g/dL, AST/ALT ≤ 3x upper limit of normal [ULN], or (≤ 5x ULN if liver metastasis present), Bilirubin ≤ 1.5x ULN, or (≤ 2.5 x ULN for subjects with Gilbert's syndrome), Albumin > 3 g/dL, Serum creatinine clearance CrCl > 30 mL/min per Cockcroft-Gault Formula, INR <1.5 unless on anticoagulants
No evidence of active infection and no serious infection within the past 30 days. Patient must have completed antibiotic course.
Mentally competent, ability to understand and willingness to sign the informed consent form and follow protocol requirements
No known central nervous system metastasis or epidural tumor
No known hypersensitivity to devimistat, platinum-based drugs, FOLFIRINOX treatment or any of their excipients
Patients must not have received any other investigational systemic agent for any indication within the past 2 weeks prior to initiation of devimistat treatment
No active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., Hemophilia A)
Female patients must not be pregnant, have a positive pregnancy test, breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 9 months after the last dose of study treatment.
Male patients must be willing to abstain from donating sperm during treatment and for 6 months after completion of study treatment
No active heart disease including but not limited to myocardial infarction that is <3 months prior to registration, symptomatic congestive heart failure (NYHA class 3 or 4), symptomatic coronary artery disease, symptomatic angina pectoris
No prior malignancy except for the following: adequately treated basal or squamous cell skin cancer, in situ cancer, localized prostate cancer (Gleason score <8), or adequately treated cancer from which the patient has been disease-free for at least 3 years prior to registration.
Patients must not be using strong CYP3A4 inducers or inhibitors (as listed in Appendix II: CYP3A4 Inducers or Inhibitors)
No marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 470 milliseconds (ms) (CTCAE grade 1) using Fridericia's QT correction formula (i.e. QTcF); or history of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome).
Patients must not have known reduced UGT1A1 or DPD activity.