Trial Title:
FL118 for Treating Patients With Advanced Pancreatic Ductal Adenocarcinoma
NCT ID:
NCT06206876
Condition:
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
Conditions: Official terms:
Adenocarcinoma
Pancreatic Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo biopsy
Arm group label:
Treatment (FL118)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood samples
Arm group label:
Treatment (FL118)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (FL118)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
DDX5 Degrader FL118
Description:
Given PO
Arm group label:
Treatment (FL118)
Other name:
FL 118
Other name:
FL-118
Other name:
FL118
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (FL118)
Other name:
Magnetic Resonance
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
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.
Detailed description:
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.
Criteria for eligibility:
Criteria:
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 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Roswell Park Cancer Institute
Address:
City:
Buffalo
Zip:
14263
Country:
United States
Contact:
Last name:
Christos Fountzilas
Phone:
716-845-8974
Email:
Christos.Fountzilas@roswellpark.org
Investigator:
Last name:
Christos Fountzilas
Email:
Principal Investigator
Start date:
October 1, 2024
Completion date:
October 1, 2027
Lead sponsor:
Agency:
Roswell Park Cancer Institute
Agency class:
Other
Source:
Roswell Park Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06206876
