Trial Title:
MK2 Inhibitor in Combination With mFOLFIRINOX for Untreated Metastatic Pancreatic Ductal Adenocarcinoma
NCT ID:
NCT06648434
Condition:
Metastatic Pancreatic Ductal Adenocarcinoma
Pancreatic Cancer
Cancer of the Pancreas
Conditions: Official terms:
Adenocarcinoma
Pancreatic Neoplasms
Conditions: Keywords:
Pancreatic cancer
Zunsemetinib
FOLFIRINOX
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Zunsemetinib
Description:
Patients 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.
Arm group label:
Dose escalation phase (zunsemetinib + mFOLFIRNOX)
Arm group label:
Dose expansion phase (zunsemetinib + mFOLFIRNOX)
Other name:
ATI-450
Intervention type:
Drug
Intervention name:
mFOLFIRINOX
Description:
Includes oxaliplatin, irinotecan, leucovorin, and 5-FU.
Arm group label:
Dose escalation phase (zunsemetinib + mFOLFIRNOX)
Arm group label:
Dose expansion phase (zunsemetinib + mFOLFIRNOX)
Summary:
The investigators hypothesize that MK2 inhibition may improve efficacy of mFOLFIRINOX
chemotherapy for patients with pancreatic ductal adenocarcinoma (PDAC).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Histologically or cytologically confirmed pancreatic ductal adenocarcinoma with no
prior systemic treatment. Patients with mixed cytology in their tumors such as
adeno-squamous, mixed neuroendocrine-carcinoma are permitted if the portion of
adenocarcinoma is predominant.
- Diagnosis of metastatic disease, where mFOLFIRINOX (or classical FOLFIRINOX) is
deemed a suitable option per the treating physician.
- Measurable disease by RECIST 1.1.
- At least 18 years and up to 75 years of age (inclusive). FOLFIRINOX or mFOLFIRINOX
carries excessive risks of toxicities for advanced aged patients. In the original
study of FOLFIRINOX versus gemcitabine1, patients above the age of 75 years were
excluded.
- ECOG performance status ≤ 1.
- Adequate bone marrow and organ function as defined below:
- Absolute neutrophil count ≥ 1.5 K/cumm
- Platelets ≥ 100 K/cumm
- Hemoglobin ≥ 9.0 g/dL
- Total bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN, unless there are liver metastases in which
case AST and ALT ≤ 5.0 x IULN
- Creatinine ≤ 1.5 x IULN or creatinine clearance > 50 mL/min by Cockcroft-Gault
- Baseline EKG with QTcF ≤ 460 ms.
- Women of childbearing potential and men who are heterosexually active must agree to
use adequate contraception as specified in the protocol. Contraception should
continue for 1 month (for women) or 3 months (for men) after the end of treatment.
Should a woman become pregnant or suspect she is pregnant while participating in
this study, she must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed
consent document (or that of legally authorized representative, if applicable).
Exclusion Criteria:
- Prior receipt of FOLFIRINOX or mFOLFIRINOX regimen for pancreatic cancer in the
adjuvant/neoadjuvant setting.
- 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.
- Currently receiving or have received 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 the agent.
- Known brain metastases or CNS involvement, because brain metastases are often
associated with poor functional status, shortened life expectancy and risk of
toxicity.
- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to zunsemetinib, or other agents used in the study.
- Clinically significant neuropathy ≥ grade 2.
- Presence of interstitial lung disease that is symptomatic or may interfere with the
detection or management of suspected treatment-related pulmonary toxicity.
- Gastrointestinal conditions which could prevent absorption of zunsemetinib, in the
opinion of the treating physician.
- Inability to swallow pills.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, or
cardiac arrhythmia .
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
serum pregnancy test within 7 days of C1D1.
- Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL
or they have a history of AIDS-defining opportunistic infection within the 12 months
prior to registration. Concurrent treatment with effective ART according to DHHS
treatment guidelines is recommended.
- Major surgery within 28 days prior to C1D1. Major surgery refers to any surgical
procedure that involves general or regional anesthesia, involves extensive resecting
or altering of body parts, carries a higher risk of complications, or requires long
recovery times.
- Use of any live vaccines against infectious diseases (eg, influenza, varicella)
within 4 weeks (28 days) of C1D1.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Contact:
Last name:
Moh'd Khushman, M.D.
Phone:
314-273-3564
Email:
mkhushman@wustl.edu
Investigator:
Last name:
Moh'd Khushman, M.D.
Email:
Principal Investigator
Investigator:
Last name:
Nikolaos Andreatos, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Olivia Aranha, M.D., Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Salman Chaudry, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Patrick Grierson, M.D., Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Michael Iglesia, M.D., Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Ramon Jin, M.D., Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Kian-Huat Lim, M.D., Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Rama Suresh, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Benjamin Tan, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Nikolaos Trikalinos, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Max Wattenberg, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Esther Lu, Ph.D.
Email:
Sub-Investigator
Start date:
December 31, 2024
Completion date:
December 31, 2029
Lead sponsor:
Agency:
Washington University School of Medicine
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Collaborator:
Agency:
Aclaris Therapeutics, Inc.
Agency class:
Industry
Source:
Washington University School of Medicine
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06648434
http://www.siteman.wustl.edu
