A Study of SLC-0111 and Gemcitabine for Metastatic Pancreatic Ductal Cancer in Subjects Positive for CAIX

Official Title

An Open-label, Multi-centre, Phase 1b Study to Investigate the Safety and Tolerability of SLC-0111 (WBI-5111) in Combination With Gemcitabine in Metastatic Pancreatic Ductal Adenocarcinoma Subjects Positive for Carbonic Anhydrase IX

Summary:

This is a multi-centre, open-label Phase 1b study of SLC-0111 (oral) in combination with IV gemcitabine in CA IX positive subjects with mPDAC and comprises of 2 parts: - Part 1: Dose Escalation - Part 2: Dose Expansion

Trial Description

Primary Outcome:

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

Secondary Outcome:

• The maximum tolerated dose [MTD] of SLC-0111 in combination with gemcitabine
• Maximum Plasma Concentration [Cmax]
• Time to Reach Maximum Plasma Concentraiton [Tmax]
• Elimination Rate Constant from the Central Compartment [Kel]
• Volume of Distribution During Terminal Phase after Intravenous Administration [Vz]
• Area Under the Concentration-Time Curve from Zero up to a Definite Time T [AUC(0-T)]
• Area Under the Concentration-Time Curve from Zero up to Infinity [AUC(0-inf)]
• Elimination Half-Life
• Determine the Recommended Phase II Dose of SLC-0111 in combination with gemcitabine
• Objective Response Rate [ORR] as Assessed by RECIST 1.1
• Progression-Free Survival [PFS] as Assessed by RECIST 1.1
• Duration of Response as Assessed by RECIST 1.1
• Overall Survival [OS]

This is a multi-centre, open-label Phase 1b study of SLC-0111 (oral) in combination with IV gemcitabine in CA IX positive subjects with mPDAC and comprises of 2 parts:

• Part 1: Dose Escalation

• Part 2: Dose Expansion Biopsy or archival tissue will be collected and tested for the presence of CAIX via Immunohistochemistry (IHC) and only subjects positive for CAIX will be enrolled in the dose-escalation and dose-expansion parts. Part 2 can only begin after a dosing regimen has been characterized in Part 1. Subjects who participated in Part 1 of study will not be eligible to participate in Part 2. The dose escalation will aim to identify the safety, tolerability and MTD of the oral formulation of SLC-0111 in combination with IV gemcitabine. Additional subjects may be enrolled at the MTD in dose expansion cohort. Data collected will allow evaluation of safety, tolerability, PK, Pharmacodynamics (PD) and tumour response of SLC-0111 in combination with gemcitabine. A traditional 3 + 3 dose escalation design will be utilized for this study. Cohorts (same dose level) of 3 to 6 evaluable subjects will participate in a dose escalation scheme in which the dose of SLC-0111 will be increased in each consecutive cohort. Dose escalation to a new cohort of subjects will occur after review of available Cycle 1 data. The dose of SLC-0111 will be escalated based on Table 1 and Table 2 in the protocol. Based on emerging data alternative dosing schedules, or dose reductions may be considered. Gemcitabine will be administered at the standard dose (1000 mg/m^2) and schedule (day 1, 8, and 15 of each cycle) but dose reductions may be considered if necessary.

• Each cohort will initially consist of up to 3 subjects.

• If none of the first 3 subjects in a cohort demonstrates dose limiting toxicities (DLTs), then the cohort will be declared safe and the next cohort will be opened for enrollment

• If 1 of the first 3 subjects in a cohort demonstrates DLTs, then 3 additional subjects will be accrued to that cohort for a total of 6 subjects

• If 1 out of 6 subjects in a cohort demonstrates DLTs, then the cohort will be declared safe and the next cohort (n=3)will be opened for enrollment

• If 2 or more subjects in a cohort demonstrates DLTs, that cohort will be declared to exceed the MTD Following the identification of a Cohort that exceeds the MTD, the next lowest dose, or an intermediate dose level may be further explored. The MTD will be defined as the highest dose level at which no more than 1 of 6 subjects demonstrates DLTs. Intra-subject dose escalation will not be allowed in this study.

View this trial on ClinicalTrials.gov