MK2 Inhibitor in Combination With mFOLFIRINOX for Untreated Metastatic Pancreatic Ductal Adenocarcinoma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorWashington University School of Medicine
About this trial
The investigators hypothesize that MK2 inhibition may improve efficacy of mFOLFIRINOX chemotherapy for patients with pancreatic ductal adenocarcinoma (PDAC).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Histologically or cytologically confirmed pancreatic ductal adenocarcinoma with no prior systemic treatment for advanced or metastatic disease. Patients with mixed cytology in their tumors such as adeno-squamous, mixed neuroendocrine-carcinoma are permitted if the portion of adenocarcinoma is predominant. Prior adjuvant/neoadjuvant therapy (including FOLFIRINOX or mFOLFIRINOX regimens) is allowed if progression occurred ≥ 12 months from the last dose of that therapy. A biopsy is not required to confirm advanced or metastatic disease.
Dose escalation: Diagnosis of advanced inoperable or metastatic disease, where mFOLFIRINOX (or classical FOLFIRINOX) is deemed a suitable option per the treating physician.
Dose expansion: Diagnosis of metastatic disease, where mFOLFIRINOX (or classical FOLFIRINOX) is deemed a suitable option per the treating physician.
Measurable disease by RECIST 1.1.
Disqualifiers
A history of other malignancy with the exception of 1) malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease; 2) or known indolent malignancies that do not require treatment and will likely not alter the course of treatment of metastatic pancreatic cancer.
History of allogeneic organ or stem cell transplant.
Currently receiving any other investigational agents, or receipt of an investigational agent within 2 weeks or 5 half-lives of the agent, whichever is shorter.
Receipt of strong and moderate CYP3A4 and CYP2C8 inhibitors (including grapefruit), strong and moderate CYP3A and CYP2C8 inducers (see Appendices H and I), and drugs with QT prolonging potential within 5 half-lives of cycle 1 day 1.
Trial design
Design model
Sequential
Treatments tested in this trial
Zunsemetinib
DrugPatients should take zunsemetinib approximately 12 hours apart (if twice daily dosing) or 24 hours apart (if once daily dosing) at the same time(s) every day, with 8 oz of water.
mFOLFIRINOX
DrugIncludes oxaliplatin, irinotecan, leucovorin, and 5-FU.
Treatment groups
51 Participants
are divided into 2 treatment groupsGroup A: Dose escalation phase (zunsemetinib + mFOLFIRNOX)Experimental treatment 2 interventions
Group B: Dose expansion phase (zunsemetinib + mFOLFIRNOX)Experimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Recommended phase II dose (RP2D) of zunsemetinib in combination with mFOLFIRINOX (Dose Escalation Only)
Time frame
Completion of 2 cycles (each cycle is 2 weeks - estimated to be 4 weeks)2
Number of participants with dose-limiting toxicities (DLTs) (Dose Escalation only)
Time frame
Completion of 2 cycles (each cycle is 2 weeks - estimated to be 4 weeks)Secondary outcomes
1
Number of participants with adverse events by types
Graded by CTCAE v5.
Time frame
From start of treatment through 30 days after last zunsemetinib dose (estimated to be 13 months)2
Progression-free rate (PFR) (only for those treated at RP2D)
Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm and/or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time frame
At 6 months3
Disease control rate (DCR) (only for those treated at RP2D)
DCR is defined as the number of participants with complete response, partial response, or stable disease) per RECIST 1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm and disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time frame
Through completion of treatment (estimated to be 12 months)4
Overall response rate (ORR) (only for those treated at RP2D)
ORR = defined as number of participants with complete response or partial response by RECIST 1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm and disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame
Through completion of treatment (estimated to be 12 months)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Washington University School of Medicine
Lead sponsor
National Cancer Institute (NCI)
Collaborator
Aclaris Therapeutics, Inc.
Collaborator
Source ClinicalTrials.gov