A Phase I/II Open Label Study to Assess Safety and Preliminary Evidence of a Therapeutic Effect of Azeliragon in Patients Refractory to Prior Treatment of Metastatic Pancreatic Cancer
Overview
- Phase
- Phase 1
- Intervention
- Azeliragon
- Conditions
- Metastatic Pancreatic Cancer
- Sponsor
- Cantex Pharmaceuticals
- Enrollment
- 30
- Locations
- 6
- Primary Endpoint
- Recommended Phase 2 Dose
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This is an open label study to determine the safety and preliminary evidence of a therapeutic effect of azeliragon in patients refractory to prior treatment of metastatic pancreatic cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient must have histologically confirmed locally advanced or metastatic adenocarcinoma of the pancreas for which potential curative measures, such as resection of an isolated metastasis, are not available.
- •Patient should have previously been treated with a Gemcitabine/Abraxane or FOLFIRINOX- based regimen.
- •Toxicity from prior chemotherapy other than alopecia has recovered to Grade ≤ 1 (CTCAE 1.0) or are at baseline (such as stable G2 neuropathy).
- •Male or non-pregnant and non-lactating female and ≥ 18 to ≤ 80 years of age.
- •Patient has adequate biological parameters as demonstrated by the following blood counts at Screening (obtained ≤ 14 days prior to enrollment) and at Baseline-Day 0: Absolute neutrophil count (ANC) ≥ 1.0 × 109/L; Platelet count ≥ 75,000/mm3 (75 × 109/L); Hemoglobin (Hgb) ≥ 9 g/dL without transfusion or growth factor support
- •Patient has the following blood chemistry levels at Screening (obtained ≤ 14 days prior to enrollment) and at Baseline-Day 0:
- •AST (SGOT), ALT (SGPT) ≤ 2.5 × upper limit of normal range (ULN), unless liver metastases are present, then ≤ 5 x ULN is acceptable. Total bilirubin ≤ 1.5 × ULN.
- •Estimated creatinine clearance of \> 60 mL/min (per Cockroft-Gault formula)
- •Patient has ECOG performance status of ≤ 2
- •Patient has been informed about the nature of the study, and has agreed to participate in the study, and signed the Informed Consent Form prior to participation in any study-related activities.
Exclusion Criteria
- •Patient has a life expectancy, per investigator assessment, of less than 3 months.
- •Patient has experienced an increase of ECOG to \> 2 between Screening and the time of first dose with study drug.
- •Patient has active, uncontrolled bacterial, or fungal infection(s) requiring systemic therapy.
- •Patients receiving CYP 2C8 inhibitors noted in Section 5.3 of the protocol.
- •Patient has a concomitant serious medical or psychiatric illness that, in the opinion of the investigator, could compromise the patient's safety or the study data integrity.
- •Patient is unwilling or unable to comply with study procedures, including, but not limited to self-administration of oral medication.
- •Patients with a gastrointestinal condition that could interfere with swallowing or absorption.
- •Females of childbearing potential who are sexually active or males with female partners of childbearing potential, where either the female or the male is unwilling to use a highly effective method of contraception during the trial and for 6 months after the last administration of study drug.
- •Patients with concurrent participation in another interventional clinical trial or use of another investigational agent within 14 days of starting study drug. Patients who are participating in non-interventional clinical trials (e.g., quality of life, imaging, observational, follow-up studies, etc.) are eligible, regardless of the timing of participation.
Arms & Interventions
Treatment Group
Azeliragon will be orally administered to 5 groups of 6 subjects, with escalation of dosing occurring with each subsequent group. Dose Level 1 is a loading dose of 15mg once daily for 6 days, followed by a dose of 5mg once daily for the rest of the study. Dose Level 2 is a loading dose of 15mg twice daily for 6 days, followed by a dose of 10mg once daily for the rest of the study. Dose Level 3 is a loading dose of 30mg twice daily for 6 days, followed by a dose of 20mg once daily for the rest of the study. Dose Level 4 is a loading dose of 30mg twice daily for 6 days, followed by a dose of 15mg twice daily for the rest of the study. Dose Level 5 is a loading dose of 30mg twice daily for 6 days, followed by a dose of 25mg twice daily for the rest of the study. Escalation will continue until stopping rules are met or the highest defined dose level is reached. The trial will be closed to accrual if the first dose level is deemed intolerable.
Intervention: Azeliragon
Outcomes
Primary Outcomes
Recommended Phase 2 Dose
Time Frame: 8 weeks
Assessment of the recommended phase 2 dose (RP2D) of azeliragon in patients with metastatic pancreatic cancer.
Secondary Outcomes
- AE and SAE Frequency(8 weeks)
- Pain after treatment initiation(8 weeks)
- Average daily opioid consumption.(8 weeks)
- Plasma CA19-9 levels(8 weeks)
- Disease Control(8 weeks)
- Overall survival(8 weeks)
- Change in Eastern Cooperative Oncology Group (ECOG) status.(8 weeks)
- Serum albumin(8 weeks)
- Body Weight(8 weeks)