Status and phase
Conditions
Treatments
About
This is a multi-center, 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:
Full description
This is a multi-center, 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:
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.
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.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Pre-Screening Inclusion Criteria:
Males or females aged ≥ 18 years old.
Able and willing to provide written pre-screening informed consent and to comply with the study protocol and procedures.
A biopsiable tumour and a willingness to provide biopsies if no archival tumour tissue exists.
Histologically or cytologically-confirmed metastatic pancreatic ductal adenocarcinoma (this can include distant lymph nodes). Subjects with locally advanced disease or regional lymph node involvement are to be excluded.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Life expectancy greater than 3 months in the investigator's opinion.
Subject (archival tissue or pre-treatment biopsy) must be positive for CAIX via IHC before screening assessments listed below begin (i.e. Study Inclusion and Exclusion Criteria)
Main Study Inclusion Criteria:
Males or females aged ≥ 18 years old.
Able and willing to provide written informed consent and to comply with the study protocol and procedures.
Histologically or cytologically-confirmed metastatic pancreatic ductal adenocarcinoma (this can include distant lymph nodes). Subjects with locally advanced disease or regional lymph node involvement are to be excluded.
≥1 prior line of systemic therapy with a 14-day washout period or if investigational combination is being considered for first line of therapy, subject was not eligible for FOLFIRINOX or gemcitabine + nab-paclitaxel.
Recovery to ≤ Grade 1 from the effects (excluding alopecia) of any prior therapy for their malignancies.
ECOG performance status 0 or 1.
Life expectancy greater than 3 months in the Investigator's opinion.
The following time must have elapsed between previous therapy for cancer or medical history event and first administration of SLC-0111 and gemcitabine:
Adequate renal function:
Adequate hepatic function:
Adequate hematologic function (without G-CSF support):
Adequate coagulation tests:
Corrected QT interval (QTc) < 470 ms
Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption.
Negative pregnancy test in female subjects of child-bearing potential (defined as women who have not undergone hysterectomy/oophorectomy or who have not been naturally post-menopausal for ≥ 12 months).
Subjects must agree not to donate gametes (oocyte or sperm) during study and for 4 months following last dose of study treatment.
Sexually active subjects (male and female) must agree to use acceptable methods of contraception to avoid pregnancy prior to start of dosing, during the course of the study and for 4 months after the last dose of study treatment.
Collect post-treatment biopsy if the tumour is biopsiable and a willingness to provide biopsies exists (optional)
Additional Inclusion Criteria for Dose Expansion (Part 2):
Exclusion Criteria:
Additional Dose Expansion Exclusion Criteria:
Subjects cannot be enrolled in the dose expansion if they were enrolled during the dose escalation of the current study.
Primary purpose
Allocation
Interventional model
Masking
6 participants in 1 patient group
Loading...
Central trial contact
Jonathan Loree, MD; Daniel J Renouf, MD
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal