Metastatic Pancreatic Ductal AdenocarcinomaPhase 2NCT07096362
Utility of ctDNA in Early Switch of First-line Chemotherapy in Metastatic Pancreatic Ductal Adenocarcinoma
A Phase 2 study testing 5-Fluorouracil, Oxaliplatin and Leucovorin in people with Metastatic Pancreatic Ductal Adenocarcinoma and Pancreatic Ductal Adenocarcinoma, run by University of Miami at 1 site in United States.
Trial summary
The purpose of this study is to understand whether a blood-based test called circulating tumor DNA (ctDNA) can detect whether participants are having a desired tumor shrinkage or an undesired lack of tumor shrinkage, and to study whether these levels of ctDNA can be used to make treatment decisions faster than the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Pancreatic Ductal Adenocarcinoma, Pancreatic Ductal Adenocarcinoma
- What is being tested?
- 5-Fluorouracil, Oxaliplatin and Leucovorin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Sep 2025to 30 Sep 2030
- Phase
- Phase 2
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
- Histologically confirmed, metastatic pancreatic adenocarcinoma. Patients with adenosquamous carcinoma and mixed adenocarcinoma/neuroendocrine carcinoma (MANEC) of the pancreas are eligible, but pure neuroendocrine neoplasms are excluded.
- Treatment-naïve patients diagnosed with metastatic pancreatic adenocarcinoma.
- Must have a detectable circulating tumor deoxyribonucleic acid (DNA) at cycle 1 day 1.
- Patients must have a detectable circulating tumor deoxyribonucleic acid (ctDNA) quantity on Northstar Response assay at baseline.
- At least one tumor measurable by Computed Tomography (CT) scan or Positron Emission Tomography-Computed Tomography (PET/CT) scan. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >20 mm with conventional techniques or >10 mm with spiral CT scan.
- Adult male and female participants (≥ 18 years of age).
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- Male or non-pregnant and non-lactating female. Men and women with intact reproductive potential must agree to use contraception.
- Adequate biological parameters as demonstrated by the following blood counts at Screening (obtained ≤ 21 days prior to enrollment) and at Baseline-Day 0:
- Absolute neutrophil count (ANC) ≥ 1.0 × 109 cells/L.
- Platelet count ≥ 100,000 cells/mm3 (100 × 109 cells/L). Supportive platelet transfusions are acceptable.
- Hemoglobin (Hgb) ≥ 9 g/dL. Supportive packed red blood cell transfusions are acceptable.
- Adequate blood chemistry levels at Screening (obtained ≤ 21 days prior to enrollment) and at Baseline-Day 0:
- Aspartate aminotransferase (AST) - serum glutamic-oxaloacetic transaminase (SGOT); alanine transaminase (ALT) - serum glutamic-pyruvic transaminase (SGPT) ≤ 2.5 × upper limit of normal (ULN) range, unless liver metastases are present, then ≤ 5 × ULN is allowed.
- Total bilirubin ≤ 1.5 × Upper Limit of Normal.
- Estimated creatinine clearance of > 60 mL/min (per Cockcroft-Gault formula).
- Albumin ≥ 3.0 g/dL.
- Eastern Cooperative Oncology Group (ECOG) performance status from 0 to ≤ 1.
- Must be a modified Folfirinox chemotherapy candidate.
- For participants not qualified or able to give legal consent, consent must be obtained from their legally authorized representative (LAR).
Who cannot join
- Patients with pure neuroendocrine neoplasms of the pancreas.
- Brain metastases.
- Uncontrolled ascites.
- Increase of ECOG to > 1 between screening and enrollment.
- Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
- History of untreated or uncontrolled HIV and/or Hepatitis B or C infection.
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- Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following:
- History of myocardial infarction, angina pectoris, symptomatic pericarditis, or coronary artery bypass graft within six months prior to study entry
- Documented cardiomyopathy
- Grade 2 or greater sensory peripheral neuropathy.
- History of chronic diarrhea.
- Pregnant or nursing.
- Concomitant serious medical or psychiatric illness that, in the opinion of the investigator, could compromise the patient's safety or integrity of the study data.
- Concurrently enrolled in any other interventional clinical protocol or investigational trial involving administration of antineoplastic compounds for the treatment of metastatic pancreatic cancer.
- Patient is unwilling or unable to comply with study procedures.
- Patients with impaired decision-making capacity.
- No other medical condition or reason that, in the opinion of the investigator, would preclude study participation.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Miami
Miami, Florida, 33136
Siudy Vasquez, (305) 243-2647, sxv507@med.miami.edu
Gretel Terrero, MD
About this study
Official title: A Phase 2 Study Assessing Utility of ctDNA in Early Switch of First-line Chemotherapy in Metastatic Pancreatic Ductal Adenocarcinoma
The purpose of this study is to understand whether a blood-based test called circulating tumor DNA (ctDNA) can detect whether participants are having a desired tumor shrinkage or an undesired lack of tumor shrinkage, and to study whether these levels of ctDNA can be used to make treatment decisions faster than the current standard approach, which is to wait 8 weeks after starting chemotherapy to obtain participant first imaging scans since starting chemotherapy.
- Being tested
- 5-Fluorouracil, Oxaliplatin, Leucovorin, Irinotecan, Gemcitabine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-FluorouracilDrug
Participants will be administered 2400 mg/m^2 of 5-Fluorouracil via continuous intravenous infusion over a 46-hour period beginning on Day 1 of each two-week cycle of standard of care (SOC) modified Folfirinox combination therapy.
OxaliplatinDrug
Participants will be administered 85 mg/m^2 of Oxaliplatin via intravenous infusion beginning on Day 1 of each two-week cycle of standard of care (SOC) modified Folfirinox combination therapy.
LeucovorinDrug
Participants will be administered 400 mg/m^2 of Leucovorin via intravenous infusion beginning on Day 1 of each two-week cycle of standard of care (SOC) modified Folfirinox combination therapy.
IrinotecanDrug
Participants will be administered 150 mg/m^2 of Irinotecan via intravenous infusion beginning on Day 1 of each two-week cycle of standard of care (SOC) modified Folfirinox combination therapy.
GemcitabineDrug
Participants will be administered 1000 mg/m^2 of Gemcitabine standard of care (SOC) via intravenous infusion on days 1, 8 and 15 of each four-week treatment cycle.
Nab PaclitaxelDrug
Participants will be administered 125 mg/m^2 of Nab Paclitaxel standard of care (SOC) by intravenous infusion on days 1, 8 and 15 of each four-week treatment cycle.
Circulating Tumor Deoxyribonucleic acid (ctDNA) AssayDiagnostic test
ctDNA will be measured in participants in person via blood samples during Screening/Baseline and at the following intervals during treatment and follow-up:
- Every weeks 2 beginning at weeks 2, 4, 6 and 8 of standard of care therapy.
- Every 4 weeks beginning at week 10 of standard of care therapy until disease progression. ctDNA will be measured to obtain participant tumor methylation scores (TMS).
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Early Switch of Chemotherapy Interventional Cohort | Experimental | Participants in this group will receive first-line chemotherapy in combination with standard of care (SOC) of 5-fluorouracil, leucovorin, irinotecan, oxaliplatin (mFOLFIRINOX) or Gemcitabine / nab-paclitaxel. Participants will receive standard of care treatment for up to 8 months.
Total participation duration is approximately 18 months. Receives: Drug: 5-Fluorouracil; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Irinotecan; Diagnostic Test: Circulating Tumor Deoxyribonucleic acid (ctDNA) Assay |
| Part 2 Arm A: Early Switch of Chemotherapy Interventional Cohort | Active comparator | Participants in this group will receive first-line chemotherapy in combination with standard of care (SOC) of 5-fluorouracil, leucovorin, irinotecan, oxaliplatin (mFOLFIRINOX) or Gemcitabine / nab-paclitaxel. After completing three cycles of therapy, participants with methylated-ctDNA fold change of less than threshold determined in Part 1 will continue to receive additional cycles of mFOLFIRINOX for up to 8 months. Participants with methylated-ctDNA fold-change of greater than threshold determined in Part 1 may switch to Part 2 Arm B.
Total participation duration is approximately 18 months. Receives: Drug: 5-Fluorouracil; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Irinotecan; Diagnostic Test: Circulating Tumor Deoxyribonucleic acid (ctDNA) Assay |
| Part 2 Arm B: Early Switch of Chemotherapy Interventional Cohort | Experimental | Participants in this group will receive first-line chemotherapy in combination with standard of care Gemcitabine and Nab-Paclitaxel therapy, after completion of up to three cycles of mFOLFIRINOX from Part 2 Arm A. Participants will receive standard of care treatment for up to 8 months.
Total participation duration is approximately 18 months. Receives: Drug: 5-Fluorouracil; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Irinotecan; Drug: Gemcitabine; Drug: Nab Paclitaxel; Diagnostic Test: Circulating Tumor Deoxyribonucleic acid (ctDNA) Assay |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1:Change in ctDNA fold-change at Week 4
Circulating tumor Deoxyribonucleic Acid (ctDNA) fold-change at week 4 is defined as the ratio between ctDNA quantity at week 4 relative to baseline. The quantity of ctDNA will be measured in ng/mL.
At week 4 among participants in Part 1 will be reported as a Tumor Methylation Score (TMS) in plasma samples. The ratio between the TMS at week 4 (TMS4) and the TMS at baseline (TMS0) will be calculated.
Measured: Baseline, Up to 4 weeks (after intervention)
Part 1: Number of Radiographic Response Status Responders vs. Number of Non-Responders
Radiographic response status among participants in Part 1 will be reported in numbers. Participants will undergo Positron Emission Tomography/Computed Tomography (PET/CT) radiographic imaging scans at the end of week 8. Participants will be subdivided into two groups: responders vs. non-responders to modified Folfirinox treatment. Responders will be defined as the number of participants achieving complete response (CR), partial response (PR) or exhibiting stable disease (SD). Non-responders will be defined as the number of participants exhibiting progressive disease (PD). Response will be evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.
Measured: Up to 1.5 years (after intervention)
Part 2: Progression-Free Survival (PFS)
Progression-Free Survival (PFS) is defined as elapsed time in months from day 1 of starting second-line (2L) chemotherapy until the date of documented progressive disease (PD) or death.
Measured: Up to 3.5 years (after intervention)
Secondary outcomes (3)
Part 1: Change in ctDNA Tumor Methylation Score (TMS)
Circulating tumor Deoxyribonucleic Acid (ctDNA) Tumor Methylation Score (TMS) is defined as the amount of methylated tumor DNA in the blood. ctDNA TMS will be assessed at baseline, weeks 2, 4, 6, and 8.
The Tumor Methylation Score (TMS) score ranges from 10 to 1,000,000. TMS is proprietary score, it does not have units. Higher TMS means higher levels of methylated tumor DNA found in the blood.
Measured: Baseline, Up to 8 weeks (after intervention)
Part 1: Number of Radiographic Responses
The number of radiographic response among participants in Part 2 will be reported as the result of Positron Emission Tomography/Computed Tomography (PET/CT) radiographic imaging scans taken at the end of week 8. Response will be evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.
Measured: Up to 8 weeks (after intervention)
Part 2: Overall Survival (OS)
Overall Survival (OS) is defined as elapsed time in months from start of first-line (1L) mFOLFIRINOX treatment to date of death.
Measured: Up to 3.5 years (after intervention)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2025
- Study start9 Sep 2025
- Primary completion30 Sep 2030 (estimated)
- Study completion30 Sep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Pancreatic Ductal AdenocarcinomaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), BillionToOne Inc.
- Responsible party
- Principal investigator, Gretel Terrero, University of Miami
- Investigators
- Gretel Terrero, MD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07096362
- Sponsor's protocol ID
- 20250087
- Other IDs
- K12CA226330, NCI-2025-06277
- Status last verified
- Sep 2026
- First submitted
- 24 Jul 2025
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No