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

University of Miami

Status and phase: Enrolling; Phase 2

Conditions: Metastatic Pancreatic Ductal Adenocarcinoma; Pancreatic Ductal Adenocarcinoma

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

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT07096362

NCI-2025-06277 (Registry Identifier)

20250087

K12CA226330 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment: 50 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 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.

2. Treatment-naïve patients diagnosed with metastatic pancreatic adenocarcinoma.

3. Must have a detectable circulating tumor deoxyribonucleic acid (DNA) at cycle 1 day 1.

4. Patients must have a detectable circulating tumor deoxyribonucleic acid (ctDNA) quantity on Northstar Response assay at baseline.

5. 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.

6. Adult male and female participants (≥ 18 years of age).

7. Male or non-pregnant and non-lactating female. Men and women with intact reproductive potential must agree to use contraception.

8. 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.

9. 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.

10. Eastern Cooperative Oncology Group (ECOG) performance status from 0 to ≤ 1.

11. Must be a modified Folfirinox chemotherapy candidate.

12. For participants not qualified or able to give legal consent, consent must be obtained from their legally authorized representative (LAR).

Exclusion criteria

1. Patients with pure neuroendocrine neoplasms of the pancreas.

2. Brain metastases.

3. Uncontrolled ascites.

4. Increase of ECOG to > 1 between screening and enrollment.

5. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.

6. History of untreated or uncontrolled HIV and/or Hepatitis B or C infection.

7. 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

8. Grade 2 or greater sensory peripheral neuropathy.

9. History of chronic diarrhea.

10. Pregnant or nursing.

11. 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.

12. Concurrently enrolled in any other interventional clinical protocol or investigational trial involving administration of antineoplastic compounds for the treatment of metastatic pancreatic cancer.

13. Patient is unwilling or unable to comply with study procedures.

14. Patients with impaired decision-making capacity.

15. No other medical condition or reason that, in the opinion of the investigator, would preclude study participation.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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50 participants in 3 patient groups

Part 1: Early Switch of Chemotherapy Interventional Cohort

Experimental group

Description:

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.

Treatment:

Drug: Oxaliplatin

Drug: Leucovorin

Drug: Irinotecan

Drug: 5-Fluorouracil

Diagnostic Test: Circulating Tumor Deoxyribonucleic acid (ctDNA) Assay

Part 2 Arm A: Early Switch of Chemotherapy Interventional Cohort

Active Comparator group

Description:

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.

Treatment:

Drug: Oxaliplatin

Drug: Leucovorin

Drug: Irinotecan

Drug: 5-Fluorouracil

Diagnostic Test: Circulating Tumor Deoxyribonucleic acid (ctDNA) Assay

Part 2 Arm B: Early Switch of Chemotherapy Interventional Cohort

Experimental group

Description:

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.

Treatment:

Drug: Nab Paclitaxel

Drug: Gemcitabine

Drug: Oxaliplatin

Drug: Leucovorin

Drug: Irinotecan

Drug: 5-Fluorouracil

Diagnostic Test: Circulating Tumor Deoxyribonucleic acid (ctDNA) Assay