FL118 for Treating Patients With Advanced Pancreatic Ductal Adenocarcinoma

NCT06206876 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: I 3555023NCI-2023-08681
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests the safety, side effects, and best dose of FL118 in treating patients with pancreatic ductal adenocarcinoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). FL118 is a small anti-tumor molecule that inhibits the expression of multiple cancer-associated anti-apoptotic proteins. An anti-apoptotic protein is a protein that interferes with or inhibits cell death. In adults, apoptosis is used to rid the body of cells that have been damaged beyond repair. Apoptosis also plays a role in preventing cancer. If apoptosis is for some reason prevented, it can lead to uncontrolled cell production that can subsequently develop into a tumor. FL118 has been shown to inhibit or block the proteins that prevent damaged/mutated (genetically changed) cells from dying, and, by doing so, prevent the growth of cancerous cells and tumor development.

Conditions

Advanced Pancreatic Ductal Adenocarcinoma; Locally Advanced Pancreatic Ductal Adenocarcinoma; Metastatic Pancreatic Ductal Adenocarcinoma; Refractory Pancreatic Ductal Adenocarcinoma; Stage II Pancreatic Cancer AJCC v8; Stage III Pancreatic Cancer AJCC v8; Stage IV Pancreatic Cancer AJCC v8; Unresectable Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (7)

• Incidence of adverse events

  Toxicity and adverse events will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

  Up to 30 days

• Maximum tolerated dose (MTD)

  The MTD will be determined from the observed dose limiting toxicities per cohort using an accelerated dose-escalation design.

  4 weeks from administation

• Recommended phase 2 dose

  The recommended phase 2 dose will be determined based on the MTD (or highest dose administered if the MTD is not reached), the pharmacokinetic/pharmacodynamic modeling, and overall clinical safety and efficacy data.

  4 weeks from administration

• Half life

  PK parameters of half-life area

  On days 1, 2, 15, and 16 of cycle 1 in dose-escalation phase

• Maximum plasma concentration

  PK parameters of maximum plasma concentration

  On days 1, 2, 15, and 16 of cycle 1 in dose-escalation phase

• Area under the curve

  PK parameter area under the curve

  On days 1, 2, 15, and 16 of cycle 1 in dose-escalation phase

• CL/F

  apparent clearance of the analyte in the plasma

  On days 1, 2, 15, and 16 of cycle 1 in dose-escalation phase

Secondary Outcomes (5)

• Pharmacodynamics parameters

  At baseline and cycle 2 day 23

• Overall response rate

  Up to 12 months

• Disease control rate

  Up to 12 months

• Progression-free survival

  From treatment until disease progression, death from disease, or last follow up, assessed up to 12 months

• Overall survival

  From treatment until death due to any cause or last follow up, assessed up to 12 months

Study Arms (1)

Treatment (FL118)

EXPERIMENTAL

Patients receive FL118 PO on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT or MRI throughout the trial. Patients may optionally undergo biopsy at screening and on study.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: DDX5 Degrader FL118; Procedure: Magnetic Resonance Imaging

Interventions

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (FL118)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (FL118)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Treatment (FL118)

DDX5 Degrader FL118 DRUG

Given PO

Also known as: FL 118, FL-118, FL118

Treatment (FL118)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (FL118)

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old
• Have a histologically or cytologically confirmed advanced PDAC (locally advanced/unresectable or metastatic for part A (dose escalation) and metastatic for part B (dose expansion)
• Progression on or intolerance to 1st line therapy for advanced disease. Note that completion of adjuvant or neoadjuvant chemotherapy within 6 months from relapsed disease is considered one line of therapy for locally advanced/unresectable or metastatic disease
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Have a life expectancy of greater than 3 months
• Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present
• Patient willing to undergo tumor biopsy at baseline and on treatment if there is a lesion that can safely be biopsied based on investigator assessment. If this is not feasible, adequate archival tumor tissue must be available
• Absolute neutrophil count (ANC): ≥ 1,500/mL
• Platelets: ≥ 100,000/mL
• Hemoglobin: ≥ 9 g/dL
• Creatinine clearance ≥ 60 mL/min (per Cockroft-Gault equation)
• Total bilirubin: ≤ 1.5 X upper limit of normal (ULN) or, direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]): ≤ 2.5 X ULN or, ≤ 5 X ULN for subjects with liver metastases
• Albumin: ≥ 3 gm/dL
• For females of reproductive potential (those who have not been surgically sterilized or have not been free from menses for \> 1 year): use of highly effective contraception for at least 1 month prior to screening and agree to use such a method during study participation and, for an additional 6 months after the end of FL118 oral administration

You may not qualify if:

• Has a major surgical procedure within 4 weeks prior to the planned first day of study drug dosing
• Received a prior treatment intended for antitumor effect (medication, surgery, radiotherapy, etc.) within 2 weeks prior to the planned first day of study drug dosing (or patient who received mitomycin C or nitrosourea within 6 weeks prior to the planned first day of study drug dosing)
• Has an active infection requiring systemic therapy
• Has a history of organ transplantation
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through the trial period after the last dose of trial treatment
• Has congestive heart failure (class III or IV New York Heart Association), acute coronary syndrome, acute cerebrovascular episode, acute peripheral vascular disease, or clinically significant cardiac arrhythmia within 6 months prior to the planned first day of study drug dosing
• Has clinically significant venous thromboembolic event (VTE), defined as lower extremity deep venous thrombosis or pulmonary embolism, within the past 3 months. Patients who are on a stable anticoagulant dose for VTE prophylaxis or treatment for at least 14 days are allowed to participate
• Bowel obstruction or perforation within the past 3 months
• Refractory malignant ascites or pleural effusions (requiring weekly para- or thoracentesis or indwelling catheter for palliation). Patients with less frequent/as needed para- or thoracentesis are allowed to participate
• Has difficulty taking oral medications, a digestive malabsorptive condition other than pancreatic exocrine insufficiency controlled with pancreatic enzyme replacement, or concurrent disease that significantly affects gastrointestinal function
• Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Biopsy; Specimen Handling; 7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Christos Fountzilas

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 6, 2023
• First Posted: January 16, 2024
• Study Start: October 1, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: January 17, 2025

Record last verified: 2025-01

Locations

US (1)