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

NCT03450018 | Terminated Phase 1

• 1 other identifier: H17-02841
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

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:

• Part 1: Dose Escalation
• Part 2: Dose Expansion

Conditions

Metastatic Pancreatic Ductal Adenocarcinoma

Keywords

Gemcitabine; SLC-0111; PDAC

Outcome Measures

Primary Outcomes (1)

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

  Adverse events (AEs) as assessed by CTCAE v5.0 will be determined by changes in safety assessments, including laboratory parameters, vital signs, ECG and physical examinations.

  Up to Safety Follow-Up Visit (30 days +/- 7 days after permanently stopping study treatment)

Secondary Outcomes (13)

• The maximum tolerated dose [MTD] of SLC-0111 in combination with gemcitabine

  Up to Safety Follow-Up Visit (30 days +/- 7 days after permanently stopping study treatment)

• Maximum Plasma Concentration [Cmax]

  Up to 4 years

• Time to Reach Maximum Plasma Concentraiton [Tmax]

  Up to 4 years

• Elimination Rate Constant from the Central Compartment [Kel]

  Up to 4 years

• Volume of Distribution During Terminal Phase after Intravenous Administration [Vz]

  Up to 4 years

Other Outcomes (2)

• Tumour Metabolic Response Using Positron Emission Tomography with 18F-FDG-PET

  Up to C3D1 +/- 7 days

• CAIX Biomarker Values

  Up to 4 years

Study Arms (1)

SLC-0111 + Gemcitabine

EXPERIMENTAL

Dose Level 1 - SLC-0111 (500 mg/day PO daily for 28 days) and Gemcitabine (1000 mg/m\^2 IV on day 1, 8, and 15) Dose Level 2 - SLC-0111 (750 mg/day PO daily for 28 days) and Gemcitabine (1000 mg/m\^2 IV on day 1, 8, and 15) Dose Level 3 - SLC-0111 (1000 mg/day PO daily for 28 days) and Gemcitabine (1000 mg/m\^2 IV on day 1, 8, and 15)

Drug: SLC-0111; Drug: Gemcitabine Injection

Interventions

SLC-0111 DRUG

Oral SLC-0111

Also known as: WBI-5111

SLC-0111 + Gemcitabine

Gemcitabine Injection DRUG

1000 mg/m\^2 IV

Also known as: Gemcitabine

SLC-0111 + Gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Regional lymph nodes are considered: Lymph nodes superior and inferior to head and body of pancreas, anterior and posterior pancreaticoduodenal, pyloric, proximal mesenteric nodes, and common bile duct lymph nodes, splenic hilar, pancreatic tail, peripancreatic, hepatic artery, infrapyloric (head only), subpyloric (head only), celiac (head only), superior mesenteric, pancreaticolienal (body and tail only), splenic (body and tail only), retroperitoneal, lateral aortic.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Life expectancy greater than 3 months in the investigator's opinion.

You may not qualify if:

• 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.
• Regional lymph nodes are considered: Lymph nodes superior and inferior to head and body of pancreas, anterior and posterior pancreaticoduodenal, pyloric, proximal mesenteric nodes, and common bile duct lymph nodes, splenic hilar, pancreatic tail, peripancreatic, hepatic artery, infrapyloric (head only), subpyloric (head only), celiac (head only), superior mesenteric, pancreaticolienal (body and tail only), splenic (body and tail only), retroperitoneal, lateral aortic.
• ≥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:
• At least 2 weeks since previous cancer-directed therapy (cytotoxic agents, targeted therapy including monoclonal antibody therapy, immunotherapy, hormonal therapy, and prior radiotherapy).
• At least 2 weeks or five times the elimination half-life (whichever is shortest) of any investigational drug/biologic or combination product prior to first dose of study treatment.
• At least 4 weeks since any major surgery
• At least 12 weeks since any incidence of severe gastrointestinal bleeding.
• Adequate renal function:
• Creatinine ≤ 1.5 times upper limit of normal (ULN) or calculated creatinine clearance (CrCl) using the Cockcroft Gault formula ≥ 60 mL/min, or measured CrCl ≥ 60 mL/min.

Sponsors & Collaborators

• British Columbia Cancer Agency: lead
• Canadian Cancer Society (CCS): collaborator
• SignalChem Lifesciences Corporation: collaborator

Study Sites (2)

BC Cancer - Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

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MeSH Terms

Interventions

SLC-0111; Gemcitabine

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Daniel J Renouf, MD

  BC Cancer - Vancouver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a traditional Phase I "3+3" study designed to identify the MTD by assessment of DLT of SLC-0111. Sample size estimates are not statistically based, but are based on acquisition of appropriate numbers of subjects to adequately describe the safety, tolerability, PK, and PD of SLC-0111 in combination with gemcitabine. Up to 18 subjects are anticipated to be enrolled in the dose escalation part; however, the actual number recruited will be dependent upon the number of dose escalations. Dose expansion (Part 2) may enroll up to 12 subjects.

Study Record Dates

• First Submitted: February 13, 2018
• First Posted: March 1, 2018
• Study Start: January 10, 2019
• Primary Completion: May 16, 2024
• Study Completion: May 16, 2024
• Last Updated: May 24, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)