The objective of study IOA-289-102 is to evaluate the safety and tolerability of escalating doses of IOA-289 in patients with metastatic pancreatic cancer in combination with standard chemotherapy consisting of gemcitabine and nab-paclitaxel. Blood and tumour samples for PK and PD will be collected and assessments for determination of any clinical efficacy will be completed.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
IOA-289 will be administered orally twice daily (BID), starting from C0D1. Gemcitabine and nab-paclitaxel will be administrated by IV infusion, weekly for 3 weeks of a 4 week cycle starting at C1D1.
UO Oncologia of Azienda Ospedaliera Universitaria Integrata di Verona
Verona, Verona, Italy
Medical Oncology and Immunotherapy Unit, University Hospital of Siena
Siena, Italy
Beatson West of Scotland Cancer Center
Glasgow, United Kingdom
Incidence of treatment-emergent adverse events [Safety and Tolerability]
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: Adverse event assessment will be assessed by CTCAE v5.0, through study completion, an average of 1 year.
Cmax
Peak plasma concentration
Time frame: at Cycle 0 Day 1 (pre-dose and 1/2/3-4/6-8hrs post-dose), and predose for Cycle 0 Day 7, Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15 and from Cycle 2 onwards Day 1 and End of Treatment. Cycle 0 is 7 days and Cycle 1 and onwards is 28 days.
Cmin
Minimum observed plasma concentration
Time frame: at Cycle 0 Day 1 (pre-dose and 1/2/3-4/6-8hrs post-dose), and predose for Cycle 0 Day 7, Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15 and from Cycle 2 onwards Day 1 and End of Treatment. Cycle 0 is 7 days and Cycle 1 and onwards is 28 days.
t½
Terminal elimination half-life
Time frame: at Cycle 0 Day 1 (pre-dose and 1/2/3-4/6-8hrs post-dose), and predose for Cycle 0 Day 7, Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15 and from Cycle 2 onwards Day 1 and End of Treatment. Cycle 0 is 7 days and Cycle 1 and onwards is 28 days.
tmax
Time of the maximum observed plasma concentration
Time frame: at Cycle 0 Day 1 (pre-dose and 1/2/3-4/6-8hrs post-dose), and predose for Cycle 0 Day 7, Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15 and from Cycle 2 onwards Day 1 and End of Treatment. Cycle 0 is 7 days and Cycle 1 and onwards is 28 days.
AUC0-t
Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: at Cycle 0 Day 1 (pre-dose and 1/2/3-4/6-8hrs post-dose), and predose for Cycle 0 Day 7, Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15 and from Cycle 2 onwards Day 1 and End of Treatment. Cycle 0 is 7 days and Cycle 1 and onwards is 28 days.
AUC0-∞
Area under the plasma concentration-time curve from time zero extrapolated to infinity
Time frame: at Cycle 0 Day 1 (pre-dose and 1/2/3-4/6-8hrs post-dose), and predose for Cycle 0 Day 7, Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15 and from Cycle 2 onwards Day 1 and End of Treatment. Cycle 0 is 7 days and Cycle 1 and onwards is 28 days.
BED
Define the biologically effective dose (BED) of IOA-289 based on available parameters
Time frame: for an average of 6 months
CA19-9
Assess changes of CA19-9 levels compared to baseline
Time frame: for an average of 6 months
LPA
Determine the PD activity of IOA-289, incl levels of LPA
Time frame: for an average of 6 months
Preliminary efficacy
Document preliminary signs of clinical efficacy of IOA-289 when given in combination with gemcitabine/nab-paclitaxel (e.g. overall response rate \[ORR\], duration of response \[DOR\], disease control rate (DCR), progression-free survival \[PFS\], and overall survival \[OS\] using RECIST v1.1)
Time frame: Imaging for RECIST assessment will start at C2D1 ±3 Days and repeated every 8 Weeks (56 ± 5Days) until disease progression.
Overall response rate [ORR]
ORR defined as percentage of patients with a CR or PR based on appropriate radiographic imaging and consistent with RECIST 1.1
Time frame: for an average of 6 months
Disease control rate [DCR]
DCR is defined as the combined percentage of patients with radiographic CR, PR and SD at different time points
Time frame: for an average of 6 months
Duration of response [DOR]
DOR defined as time from first documented evidence of CR or PR until disease progression or death from any cause among patients who achieve objective response
Time frame: for an average of 6 months
Progression free survival [PFS]
PFS defined as the time from the date of the first dose of study treatment until the earliest date of disease progression as determined by radiographic disease assessment
Time frame: for an average of 6 months
Overall survival [OS]
OS defined as the time from the date of the first dose of study treatment until death from any cause.
Time frame: for an average of 6 months