Advanced Pancreatic Ductal AdenocarcinomaPhase 1NCT06206876
FL118 for Treating Patients With Advanced Pancreatic Ductal Adenocarcinoma
A Phase 1 study testing Biopsy, Biospecimen Collection and Computed Tomography in people with Advanced Pancreatic Ductal Adenocarcinoma and Locally Advanced Pancreatic Ductal Adenocarcinoma, run by Roswell Park Cancer Institute at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Pancreatic Ductal Adenocarcinoma, Locally Advanced Pancreatic Ductal Adenocarcinoma, Metastatic Pancreatic Ductal Adenocarcinoma
- What is being tested?
- Biopsy, Biospecimen Collection and Computed Tomography
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2025to 1 Oct 2027
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Roswell Park Cancer Institute
Buffalo, New York, 14263
About this study
Official title: First-in-Human Phase I Trial of FL118 in Patients With Advanced Pancreatic Ductal Adenocarcinoma
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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:
- 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.
- 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
- Being tested
- Biopsy, Biospecimen Collection, Computed Tomography, DDX5 Degrader FL118, Magnetic Resonance Imaging
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BiopsyProcedure or surgery
Also called BIOPSY_TYPE, Bx
Undergo biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo collection of blood samples
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
DDX5 Degrader FL118Drug
Also called FL 118, FL-118, FL118
Given PO
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Undergo MRI
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: DDX5 Degrader FL118; Procedure: Magnetic Resonance Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 4 weeks from administration
Half life
PK parameters of half-life area
Measured: On days 1, 2, 15, and 16 of cycle 1 in dose-escalation phase
Maximum plasma concentration
PK parameters of maximum plasma concentration
Measured: On days 1, 2, 15, and 16 of cycle 1 in dose-escalation phase
Area under the curve
PK parameter area under the curve
Measured: On days 1, 2, 15, and 16 of cycle 1 in dose-escalation phase
CL/F
apparent clearance of the analyte in the plasma
Measured: On days 1, 2, 15, and 16 of cycle 1 in dose-escalation phase
Secondary outcomes (5)
Pharmacodynamics parameters
Will be collected at baseline and day 23
Measured: At baseline and cycle 2 day 23
Overall response rate
Will be assessed use a two-stage, single-arm Simon minimax design.
Measured: Up to 12 months
Disease control rate
The disease control (complete response + partial response + stable disease) will be summarized using frequencies and relative frequencies. The disease control rate will be estimated with a 95% credible region obtained by Jeffrey's prior method.
Measured: Up to 12 months
Progression-free survival
Will be summarized using standard Kaplan-Meier methods, where estimates of median survival will be obtained with 95% confidence intervals.
Measured: From treatment until disease progression, death from disease, or last follow up, assessed up to 12 months
Overall survival
Will be summarized using standard Kaplan-Meier methods, where estimates of median survival will be obtained with 95% confidence intervals.
Measured: From treatment until death due to any cause or last follow up, assessed up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2024
- Study start1 Oct 2025 (estimated)
- Primary completion1 Oct 2027 (estimated)
- Study completion1 Oct 2027 (estimated)
Why it stopped: never opened
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Pancreatic Ductal AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by Roswell Park Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Roswell Park Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christos Fountzilas, Principal investigator, Roswell Park Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06206876
- Sponsor's protocol ID
- I 3555023
- Other IDs
- NCI-2023-08681, I 3555023
- Status last verified
- Jan 2025
- First submitted
- 6 Dec 2023
- Last updated
- 17 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- First-in-Human Phase I Trial of FL118 in Patients With Advanced Pancreatic Ductal Adenocarcinoma
- ClinicalTrials.gov ID
- NCT06206876
- Acronym / sponsor ID
- I 3555023
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: never opened
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Roswell Park Cancer InstituteUniversity, hospital or other
- Study start
- 1 Oct 2025 (estimated)
- Primary completion
- 1 Oct 2027 (estimated)
- Study completion
- 1 Oct 2027 (estimated)
- First posted
- 16 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (FL118) | Experimental | Procedure: Biopsy, Procedure: Biospecimen Collection, Procedure: Computed Tomography, Drug: DDX5 Degrader FL118, Procedure: Magnetic Resonance ImagingPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BiopsyAlso: BIOPSY_TYPE, BxUndergo biopsy | Procedure or surgery | Treatment (FL118) |
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Specimen CollectionUndergo collection of blood samples | Procedure or surgery | Treatment (FL118) |
| Computed TomographyAlso: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial TomographyUndergo CT | Procedure or surgery | Treatment (FL118) |
| DDX5 Degrader FL118Also: FL 118, FL-118, FL118Given PO | Drug | Treatment (FL118) |
| Magnetic Resonance ImagingAlso: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic ResonanceUndergo MRI | Procedure or surgery | Treatment (FL118) |
Primary outcome
Incidence of adverse events
Time frame: Up to 30 days
Toxicity and adverse events will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Maximum tolerated dose (MTD)
Time frame: 4 weeks from administation
The MTD will be determined from the observed dose limiting toxicities per cohort using an accelerated dose-escalation design.
Recommended phase 2 dose
Time frame: 4 weeks from administration
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.
Half life
Time frame: On days 1, 2, 15, and 16 of cycle 1 in dose-escalation phase
PK parameters of half-life area
Maximum plasma concentration
Time frame: On days 1, 2, 15, and 16 of cycle 1 in dose-escalation phase
PK parameters of maximum plasma concentration
Area under the curve
Time frame: On days 1, 2, 15, and 16 of cycle 1 in dose-escalation phase
PK parameter area under the curve
CL/F
Time frame: On days 1, 2, 15, and 16 of cycle 1 in dose-escalation phase
apparent clearance of the analyte in the plasma
5 secondary outcomes
Pharmacodynamics parameters
Time frame: At baseline and cycle 2 day 23
Overall response rate
Time frame: Up to 12 months
Disease control rate
Time frame: Up to 12 months
Progression-free survival
Time frame: From treatment until disease progression, death from disease, or last follow up, assessed up to 12 months
Overall survival
Time frame: From treatment until death due to any cause or last follow up, assessed up to 12 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christos Fountzilas principal investigator
Roswell Park Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Biopsy, Biospecimen Collection and Computed Tomography in people with Advanced Pancreatic Ductal Adenocarcinoma and Locally Advanced Pancreatic Ductal Adenocarcinoma, run by Roswell Park Cancer Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 17 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (time frame: Up to 30 days). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jan 2025.