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

July 31, 2023 updated by: University of Michigan Rogel Cancer Center

A Multicenter Open-Label Dose Optimization Trial of Devimistat in Combination With Modified FOLFIRINOX in Patients With Metastatic Adenocarcinoma of the Pancreas

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Rogel Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: TiTE-CRM Dose Escalation
Devimistat at Dose Level IV 2 hrs + modified FOLFIRINOX
Drug: Devimistat
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
Drug: Modified FOLFIRINOX
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
Experimental: Expansion Cohort A
Devimistat 500 mg/m2 IV 2 hrs + modified FOLFIRINOX
Drug: Devimistat
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
Drug: Modified FOLFIRINOX
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
Experimental: Expansion Cohort B
Devimistat at MTD IV 4 hrs + modified FOLFIRINOX
Drug: Devimistat
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
Drug: Modified FOLFIRINOX
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
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
Time Frame: 15 days post the start of combination therapy
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
Time Frame: 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.
up to 42 months after enrollment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of subjects with reported adverse events and reportable serious events
Time Frame: 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).
up to 25 months after enrollment
Overall Response Rate (ORR) of devimistat plus modified FOLFIRINOX
Time Frame: up to 42 months after enrollment
ORR will be determined as per the RECISTv1.1 criteria
up to 42 months after enrollment
Overall Survival (OS) of devimistat plus modified FOLFIRINOX
Time Frame: up to 42 months after enrollment
OS will be defined from the date of initial treatment to either date of death or censoring.
up to 42 months after enrollment
Overall Survival (OS) of devimistat plus modified FOLFIRINOX based on gender
Time Frame: up to 42 months after enrollment
OS will be defined from the date of initial treatment to either date of death or censoring.
up to 42 months after enrollment
Duration of response (DoR) of devimistat plus modified FOLFIRINOX
Time Frame: 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.
up to 42 months after enrollment
To assess pharmacokinetics (Cmax) of devimistat
Time Frame: 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)
up to 42 months after enrollment
To assess pharmacokinetics (AUCinf) of devimistat
Time Frame: 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)
up to 42 months after enrollment
To assess pharmacokinetics (t1/2) of devimistat
Time Frame: 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)
up to 42 months after enrollment
To assess pharmacokinetics (tmax) of devimistat
Time Frame: 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)
up to 42 months after enrollment
To assess pharmacokinetics (CL) of devimistat
Time Frame: up to 42 months after enrollment
The PK parameters of devimistat (and its metabolites, if appropriate), including but not limited to clearance (CL)
up to 42 months after enrollment
To assess pharmacokinetics (Vd) of devimistat
Time Frame: 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)
up to 42 months after enrollment
To determine the median Progression Free Survival (PFS) of devimistat plus modified FOLFIRINOX based on gender
Time Frame: 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.
up to 42 months after enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Michigan Rogel Cancer Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Vaibhav Sahai, University of Michigan Rogel Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 23, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 26, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 3, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 2, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 31, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UMCC 2022.126
  • HUM00228911 (Other Identifier: University of Michigan)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Investigators interested in data would email the study PI

IPD Sharing Time Frame

After study publication

IPD Sharing Access Criteria

Investigators interested in data would email the study PI

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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