Pancreatic Cancer Metastatic
Conditions
Keywords
pancreatic cancer, PDAC, Pancreatic Ductal Adenocarcinoma
Brief summary
This study is testing narmafotinib, a type of drug called a focal adhesion kinase (FAK) inhibitor, when it is given in combination with 4 chemotherapy drugs in a regimen called FOLFIRINOX, to patients who have pancreatic cancer which has metastasised (spread). The study is being run in 2 parts. Part A will test increasing dose levels of narmafotinib in at least 3 people per dose at up to 4 dose levels to assess safety. Part B will test 2 of the dose levels from Part A in 20 people per dose, to select the best dose to take forward into future studies. Participants will take narmafotinib as oral capsules every day. They will also receive mFOLFIRINOX chemotherapy on Day 1 and and Day 15 of 28-day cycles.
Interventions
DRUGnarmafotinib ascending doses
once daily capsules
DRUGnarmafotinib dose comparison
once daily capsules
Sponsors
Amplia Therapeutics Limited
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part A - dose ascending BOIN design Part B - parallel arm (2 dose levels)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Aged at least 18 years at the time of consent. * Confirmed diagnosis of metastatic pancreatic adenocarcinoma (PDAC) within the 6 weeks prior to study start and have not received 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 * Have a life expectancy of \> 3 months. * Adequate organ function * Agree to use effective contraception.
Exclusion criteria
* Pregnant or breast-feeding * Have 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. * Conditions that could interfere with the swallowing or absorption of study medication. * Received previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease. * Received cytotoxic doses of any 5-FU based chemotherapy. * Any chemotherapy related toxicities greater than grade 1 from prior neoadjuvant or adjuvant therapy for PDAC. * Human immunodeficiency virus (HIV) infection and/or history of Hepatitis B infection or known to have active hepatitis B or C. * 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, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis. * Clinical signs of active infection at the time of Screening or Baseline. * Clinically significant allergies to narmafotinib, mFOLFIRINOX components (or any of their excipients) that are not likely to be well controlled with pre-medication or other supportive measures. * Any of the conditions or events outlined in the Contraindications or Special Warnings and Precautions sections of the mFOLFIRINOX component package inserts. * Peripheral neuropathy \> Grade 1. * Prior treatment with narmafotinib or other FAK inhibitor within the 2 years prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Treatment-Emergent Adverse Events (TEAEs) from Baseline to End of Study | From first dose of study drug to end of study, an expected average of 6 months | TEAEs during study treatment and follow up periods |
| Part B: identification of optimal dose of narmafotinib | From first dose of study drug to end of study, an expected average of 6 months | The optimal dose will be selected based on a review of safety, pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and any other available relevant data |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| narmafotinib levels in plasma | Days -7, -6, -1, 1 and 15 of Run-In/Cycle 1; and Day 1 of Cycles 2 and 4 (each cycle is 28 days) | Measurement of maximum concentration (Cmax) of narmafotinib |
| Overall response rate (ORR) | Imaging every 56 days per participant, with an expected average duration of 6 months | ORR based on RECIST 1.1 |
| Overall survival (OS) | Imaging every 56 days per participant, with an expected average duration of 6 months | OS of participants, defined as time from first dose until death from any cause |
| Progression free survival (PFS) | Imaging every 56 days per participant, with an expected average duration of 6 months | PFS of participants, defined as time from first dose to date of first observed progression, based on RECIST, or death from any cause (whichever comes first) |
| Clinical benefit rate (CBR) | Imaging every 56 days per participant, with an expected average duration of 6 months | CBR defined as the proportion of patients with complete response (CR) + partial response (PR) + stable disease (SD) with SD for at least 6 months |
| Duration of response (DOR) | Imaging every 56 days per participant, with an expected average duration of 6 months | DOR based on RECIST defined as the time from the date of the first confirmed response to the date of progression or death |
| Disease control rate (DCR) | Imaging every 56 days per participant, with an expected average duration of 6 months | DCR based on RECIST defined as the proportion of participants who achieve complete response (CR), partial response (PR) or stable disease (SD) |
Countries
Australia
Outcome results
None listed