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

NCT ID: NCT07096362

Last Updated: 2025-09-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-09
• Study Completion Date: 2030-09-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Early Switch of Chemotherapy Interventional Cohort

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.

Group Type: EXPERIMENTAL

5-Fluorouracil

Intervention Type: 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.

Oxaliplatin

Intervention Type: 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.

Leucovorin

Intervention Type: 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.

Irinotecan

Intervention Type: 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.

Circulating Tumor Deoxyribonucleic acid (ctDNA) Assay

Intervention Type: 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 2 Arm A: Early Switch of Chemotherapy Interventional Cohort

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.

Group Type: ACTIVE_COMPARATOR

5-Fluorouracil

Intervention Type: 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.

Oxaliplatin

Intervention Type: 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.

Leucovorin

Intervention Type: 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.

Irinotecan

Intervention Type: 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.

Circulating Tumor Deoxyribonucleic acid (ctDNA) Assay

Intervention Type: 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 2 Arm B: Early Switch of Chemotherapy Interventional Cohort

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.

Group Type: EXPERIMENTAL

5-Fluorouracil

Intervention Type: 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.

Oxaliplatin

Intervention Type: 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.

Leucovorin

Intervention Type: 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.

Irinotecan

Intervention Type: 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.

Gemcitabine

Intervention Type: 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.

Nab Paclitaxel

Intervention Type: 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.

Circulating Tumor Deoxyribonucleic acid (ctDNA) Assay

Intervention Type: 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).

Interventions

5-Fluorouracil

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.

Intervention Type: DRUG

Oxaliplatin

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.

Intervention Type: DRUG

Leucovorin

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.

Intervention Type: DRUG

Irinotecan

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.

Intervention Type: DRUG

Gemcitabine

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.

Intervention Type: DRUG

Nab Paclitaxel

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.

Intervention Type: DRUG

Circulating Tumor Deoxyribonucleic acid (ctDNA) Assay

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).

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Miami

OTHER

Sponsor Role: lead

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

BillionToOne, Inc

UNKNOWN

Sponsor Role: collaborator

Responsible Party

Gretel Terrero

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gretel Terrero, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

University of Miami

Miami, Florida, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Siudy Vasquez

Role: CONTACT

sxv507@med.miami.edu

(305) 243-2647

Facility Contacts

Siudy Vasquez

Role: primary

sxv507@med.miami.edu

(305) 243-2647

Other Identifiers

K12CA226330

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2025-06277

Identifier Type: REGISTRY

Identifier Source: secondary_id

20250087

Identifier Type: -

Identifier Source: org_study_id