FL118 for Treating Patients With Advanced Pancreatic Ductal Adenocarcinoma

Brief summary public domain (ClinicalTrials.gov)

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.

Detailed description public domain (ClinicalTrials.gov)

PRIMARY OBJECTIVES: I. To establish the safety, schedule, and dosing of DDX5 degrader FL118 (FL118) in patients with advanced pancreatic ductal adenocarcinoma (PDAC). II. To determine the pharmacokinetics (PK) of FL118 in patients with advanced PDAC. SECONDARY OBJECTIVES: I. To determine the pharmacodynamics (PD) of FL118 in patients with advanced PDAC. II. To determine the preliminary antineoplastic efficacy of FL118 in patients with advanced PDAC. EXPLORATORY OBJECTIVES: I. To evaluate biomarkers predictive of response or resistance. II. Evaluate changes in the tumor microenvironment. III. To determine the significance of somatic and germline DNA damage repair mutations as predictive biomarkers of antineoplastic activity. OUTLINE: This is a dose-escalation study of FL118 followed by a dose-expansion study. Patients receive FL118 orally (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 computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial. Patients may optionally undergo biopsy at screening and on study. After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 12 months.

Intervention public domain (ClinicalTrials.gov)

Procedure: Biopsy. Undergo biopsy

Intervention public domain (ClinicalTrials.gov)

Procedure: Biospecimen Collection. Undergo collection of blood samples

Intervention public domain (ClinicalTrials.gov)

Procedure: Computed Tomography. Undergo CT

Intervention public domain (ClinicalTrials.gov)

Drug: DDX5 Degrader FL118. Given PO

Intervention public domain (ClinicalTrials.gov)

Procedure: Magnetic Resonance Imaging. Undergo MRI

Arm public domain (ClinicalTrials.gov)

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.

Primary outcome public domain (ClinicalTrials.gov)

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. Time frame: Up to 30 days.

Primary outcome public domain (ClinicalTrials.gov)

Maximum tolerated dose (MTD). The MTD will be determined from the observed dose limiting toxicities per cohort using an accelerated dose-escalation design. Time frame: 4 weeks from administation.

Primary outcome public domain (ClinicalTrials.gov)

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. Time frame: 4 weeks from administration.

Primary outcome public domain (ClinicalTrials.gov)

Half life. PK parameters of half-life area Time frame: On days 1, 2, 15, and 16 of cycle 1 in dose-escalation phase.

Primary outcome public domain (ClinicalTrials.gov)

Maximum plasma concentration. PK parameters of maximum plasma concentration Time frame: On days 1, 2, 15, and 16 of cycle 1 in dose-escalation phase.

Secondary outcome public domain (ClinicalTrials.gov)

Pharmacodynamics parameters. Time frame: At baseline and cycle 2 day 23.

Secondary outcome public domain (ClinicalTrials.gov)

Overall response rate. Time frame: Up to 12 months.

Secondary outcome public domain (ClinicalTrials.gov)

Disease control rate. Time frame: Up to 12 months.

Secondary outcome public domain (ClinicalTrials.gov)

Progression-free survival. Time frame: From treatment until disease progression, death from disease, or last follow up, assessed up to 12 months.

Secondary outcome public domain (ClinicalTrials.gov)

Overall survival. Time frame: From treatment until death due to any cause or last follow up, assessed up to 12 months.

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: * 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 * For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner during the study participation and for an additional 3 months after the end of FL118 oral administration * Be willing and able to comply with all study procedures and, availability for the duration of the study * Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: * Has a major surgical procedure within 4 weeks prior to the planned first day …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 0 participants (actual).

Why stopped public domain (ClinicalTrials.gov)

never opened