Utility of ctDNA in Early Switch of First-line mFOLFIRINOX in Metastatic Pancreatic Ductal Adenocarcinoma

NCT07096362 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 20250087K12CA226330NCI-2025-06277
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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 current standard approach, which is to wait 8 weeks after starting chemotherapy to obtain participant first imaging scans since starting chemotherapy.

Conditions

Metastatic Pancreatic Ductal Adenocarcinoma; Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  Up to 3.5 years (after intervention)

Secondary Outcomes (3)

• Part 1: Change in ctDNA Tumor Methylation Score (TMS)

  Baseline, Up to 8 weeks (after intervention)

• Part 1: Number of Radiographic Responses

  Up to 8 weeks (after intervention)

• Part 2: Overall Survival (OS)

  Up to 3.5 years (after intervention)

Study Arms (3)

Part 1: Early Switch of Chemotherapy Interventional Cohort

EXPERIMENTAL

Participants in this group will receive ctDNA monitoring in combination with standard of care (SOC) of 5-fluorouracil, leucovorin, irinotecan, oxaliplatin (mFOLFIRINOX). Participants will receive standard of care treatment for up to 8 months. Total participation duration is approximately 18 months.

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 ctDNA monitoring in combination with standard of care (SOC) of 5-fluorouracil, leucovorin, irinotecan, oxaliplatin (mFOLFIRINOX). 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.

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 ctDNA monitoring 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.

Drug: 5-Fluorouracil; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Irinotecan; Drug: Gemcitabine; Drug: Nab Paclitaxel; Diagnostic Test: Circulating Tumor Deoxyribonucleic acid (ctDNA) Assay

Interventions

5-Fluorouracil DRUG

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.

Part 1: Early Switch of Chemotherapy Interventional Cohort; Part 2 Arm A: Early Switch of Chemotherapy Interventional Cohort; Part 2 Arm B: Early Switch of Chemotherapy Interventional Cohort

Oxaliplatin DRUG

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.

Part 1: Early Switch of Chemotherapy Interventional Cohort; Part 2 Arm A: Early Switch of Chemotherapy Interventional Cohort; Part 2 Arm B: Early Switch of Chemotherapy Interventional Cohort

Leucovorin DRUG

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.

Part 1: Early Switch of Chemotherapy Interventional Cohort; Part 2 Arm A: Early Switch of Chemotherapy Interventional Cohort; Part 2 Arm B: Early Switch of Chemotherapy Interventional Cohort

Irinotecan DRUG

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.

Part 1: Early Switch of Chemotherapy Interventional Cohort; Part 2 Arm A: Early Switch of Chemotherapy Interventional Cohort; Part 2 Arm B: Early Switch of Chemotherapy Interventional Cohort

Gemcitabine DRUG

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.

Part 2 Arm B: Early Switch of Chemotherapy Interventional Cohort

Nab Paclitaxel DRUG

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.

Part 2 Arm B: Early Switch of Chemotherapy Interventional Cohort

Circulating Tumor Deoxyribonucleic acid (ctDNA) Assay DIAGNOSTIC_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).

Part 1: Early Switch of Chemotherapy Interventional Cohort; Part 2 Arm A: Early Switch of Chemotherapy Interventional Cohort; Part 2 Arm B: Early Switch of Chemotherapy Interventional Cohort

Eligibility Criteria

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

You may qualify if:

• 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).
• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University of Miami: lead
• National Cancer Institute (NCI): collaborator
• BillionToOne, Inc: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

RECRUITING

MeSH Terms

Interventions

Fluorouracil; Oxaliplatin; Leucovorin; Irinotecan; Gemcitabine; Taxes

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Camptothecin; Alkaloids; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Economics; Health Care Economics and Organizations

Study Officials

• Gretel Terrero, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Siudy Vasquez

CONTACT

(305) 243-2647; sxv507@med.miami.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 24, 2025
• First Posted: July 31, 2025
• Study Start: September 9, 2025
• Primary Completion (Estimated): September 30, 2030
• Study Completion (Estimated): September 30, 2030
• Last Updated: September 23, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)