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

ConditionsMetastatic Pancreatic Ductal AdenocarcinomaPancreatic Ductal Adenocarcinoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Miami

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

Patients with pure neuroendocrine neoplasms of the pancreas.

Brain metastases.

Uncontrolled ascites.

Increase of ECOG to > 1 between screening and enrollment.

Trial design

Design model

Sequential

Treatments tested in this trial

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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).

Treatment groups

50 Participants
are divided into 3 treatment groups
Group A: Part 1: Early Switch of Chemotherapy Interventional CohortExperimental treatment 5 interventions
Group B: Part 2 Arm A: Early Switch of Chemotherapy Interventional CohortActive comparator 5 interventions
Group C: Part 2 Arm B: Early Switch of Chemotherapy Interventional CohortExperimental treatment 7 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
Baseline, Up to 4 weeks (after intervention)
2

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.

Time frame
Up to 1.5 years (after intervention)
3

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.

Time frame
Up to 3.5 years (after intervention)

Secondary outcomes

1

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.

Time frame
Baseline, Up to 8 weeks (after intervention)
2

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.

Time frame
Up to 8 weeks (after intervention)
3

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.

Time frame
Up to 3.5 years (after intervention)

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Miami

Lead sponsor

National Cancer Institute (NCI)

Collaborator

BillionToOne Inc.

Collaborator

Source ClinicalTrials.gov
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