IRB Study Number 25-1066
Status Recruiting
Phases Phase 1, Phase 2
Location Cleveland Clinic Main Campus
Institute Taussig Cancer Institute
Description
Part A: Pharmacokinetics, Safety and Tolerability
Primary Objective:
• To assess the safety and tolerability of oral narmafotinib administered with modified FOLFIRINOX (mFOLFIRINOX) in participants with pancreatic cancer.
Secondary Objectives:
• To assess the pharmacokinetics (PK) of narmafotinib and major metabolite M4 when narmafotinib is administered with mFOLFIRINOX in participants with pancreatic cancer.
• To assess the efficacy of oral narmafotinib when administered with mFOLFIRINOX in participants with pancreatic cancer.
Exploratory objectives:
• To assess the effects of narmafotinib administered with mFOLFIRINOX on CA19-9 and other biomarkers in participants with pancreatic cancer.
• To assess biological factors associated with antitumor activity in tumor samples.
Part B: Efficacy
Primary Objective:
• To determine the optimal dose of narmafotinib for future studies.
Secondary Objectives:
• To assess the safety and tolerability of oral narmafotinib administered with mFOLFIRINOX in participants with pancreatic cancer.
• To assess the efficacy of oral narmafotinib administered with mFOLFIRINOX by Overall Objective Response Rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in participants with pancreatic cancer.
• To assess overall survival (OS) and progression free survival (PFS) in pancreatic cancer patients administered oral narmafotinib with mFOLFIRINOX.
• To assess the PK of narmafotinib and M4 when narmafotinib is administered with mFOLFIRINOX in participants with pancreatic cancer.
• To assess the duration of response (DOR) based on RECIST v1.1.
• To assess the clinical benefit rate (CBR) based on RECIST v1.1.
• To assess the disease control rate (DCR) based on RECIST v1.1.
Exploratory Objectives:
• To assess the effects of narmafotinib on pFAK in participants with pancreatic cancer.
• To assess the effects of narmafotinib administered with mFOLFIRINOX on CA19-9 and other biomarkers in participants with pancreatic cancer.
• To assess biological factors associated with antitumor activity in tumor samples.
Inclusion Criteria
- Provide written informed consent prior to any study procedures and agree to adhere to all protocol requirements.
- Aged at least 18 years at the time of consent.
- Confirmed histological or cytological diagnosis of metastatic pancreatic adenocarcinoma, with initial diagnosis of metastatic disease ≤ 6 weeks prior to Day –7 and no prior treatment for metastatic PDAC.
- Have measurable disease by RECIST v1.1.
- Eligible for treatment with mFOLFIRINOX as standard of care therapy.
- Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1, as determined within 72 hours prior to the 1st dose of narmafotinib and with no deterioration in ECOG over the previous 2 weeks.
- Have a life expectancy of > 3 months.
- Adequate organ function, as defined by the laboratory results below (samples must be obtained ≤ 14 days prior to Day -7):
a. Hematology:
i. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
ii. Platelet count ≥ 100,000/mm3 (100 × 109/L)
iii. Hemoglobin (Hb) ≥ 10 g/dL.
b. Serum chemistry:
i. Aspartate transaminase (AST / SGOT), alanine transaminase (ALT / SGPT) ≤ 2.5 × upper limit of normal range (ULN), unless liver metastases are clearly present, then ≤ 5 × ULN is allowed.
ii. Total bilirubin ≤ 1.5 x ULN
iii. Albumin ≥ 30g/L
iv. Creatinine clearance > 60 mL/min (calculated using the Cockcroft -Gault equation).
c. No clinically significant abnormalities in coagulation results.
d. No clinically significant abnormalities in urinalysis results. - Agree to use contraception according to protocol.
Exclusion Criteria
- Pregnant, breast-feeding, or plans to become pregnant during the study.
- Has received any investigational medicinal product (IMP) within 30 days or 5 half-lives (whichever is longer) prior to Day -7.
- Neuroendocrine or acinar cell pancreas tumors.
- Known brain metastases.
- Gastrointestinal condition that could interfere with the swallowing or absorption of study medication, including chronic diarrhea or inflammatory disease of the colon or rectum.
- Use or intend to use any prescription or non-prescription antacids or H2 blockers within 2 days prior to first dose of narmafotinib and within 10 hours prior to narmafotinib dosing, or any use of proton pump inhibitors during the study.
- Have received previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease, except placement of a biliary stent which is permitted.
- Participants having received cytotoxic doses of any of the components of mFOLFIRINOX are not eligible for this study. Prior treatment with single agent 5-FU administered exclusively as a radiation sensitizer in the neoadjuvant or adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no toxicities greater than grade 1 are still present.
- Any chemotherapy related toxicities greater than grade 1 from prior neoadjuvant or adjuvant therapy for PDAC.
- Patients with prior history of other malignancies in the past 5-years except in situ cancer or curatively treated basal or squamous cell skin cancer.
- Major surgery, other than diagnostic surgery (i.e., surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day -7.
- Confirmed human immunodeficiency virus (HIV) infection and/or history of Hepatitis B infection or known to have active hepatitis B or C. Subjects with hepatitis C who have been clinically cured (defined as persistent absence of hepatitis C RNA with polymerase chain reaction testing of serum after 12 weeks from completing antiviral treatment) are eligible for this study.
- Known history of uncontrolled angina, myocardial infarction, coronary stenting, stroke, or cerebrovascular accident within 1-year prior to the first dose of study drug.
- History of interstitial lung disease, slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or pulmonary hypersensitivity pneumonitis
- History of multiple allergies that in the opinion of the Investigator deems the patient unsuitable.
