Adjuvant Pancreatic Therapy Guided by MRD
ConditionPancreatic Adenocarcinoma Resectable
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-75
SponsorRuijin Hospital
About this trial
Pancreatic adenocarcinoma (PAAD) is a leading cause of cancer-related deaths worldwide. Although surgical resection can be curative, the 5-year overall survival (OS) rate after resection alone is approximately 20%. Adjuvant chemotherapy can improve survival outcomes in patients with resected PAAD. This study will explore the application of ctDNA MRD in guiding adjuvant therapy in these patients.
This prospective, randomized, interventional trial will evaluate a ct-DNA MRD-guided adjuvant therapy strategy in PAAD patients who have undergone radical resection at our institution. Prior to adjuvant chemotherapy, patients will be randomized (1:1) to either the experimental arm (Arm A) or the control arm (Arm B). Arm A will receive ct-DNA MRD-guided therapy, while Arm B will receive non-ctDNA-driven standard of care post-operative adjuvant therapy.
In Arm A, patients will receive a physician-selected, guideline-recommended adjuvant therapy regimen in 12-week cycles. ctDNA MRD will be assessed before the end of first cycle and at weeks 8 and 11. If two consecutive post-treatment MRD tests are negative, therapy will be "de-escalated" (discontinued) with regular follow-up as determined by the clinician. Otherwise, another treatment cycle will be administered, with the same MRD assessment. Following the second cycle, patients without two negative MRD results (only tested at week 8 and week 11 within each cycle) will "escalate" to a longer duration of chemotherapy (comparing to the 6-month standard of care) at the clinician's discretion. Treatment will continue until disease progression, intolerance, or study termination.
Arm B will receive standard post-operative adjuvant therapy for a duration recommended by CSCO guidelines (typically 6 months), followed by regular follow-up every 8 weeks.
The primary endpoint is to compare the prognosis, tolerability, and treatment completion rates between the two arms.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Capable of providing written informed consent (ICF) and able to understand and agree to comply with the study requirements and assessment schedule
Male or female aged 18-75 years at the time of ICF signing.
Histologically confirmed pancreatic ductal adenocarcinoma, Stage I-III, and has undergone R0 resection.
Time between surgery and randomization ≤ 12 weeks.
Disqualifiers
Other types of non-ductal pancreatic tumors, including neuroendocrine tumors or acinar cell carcinoma, cystadenocarcinoma, and ampullary carcinoma.
Hepatic or renal dysfunction as follows, or if the investigator considers adjuvant chemotherapy to be clearly contraindicated: a) Moderate/severe renal impairment (GFR < 30 ml/min) calculated using the Cockcroft-Gault equation. b) Absolute neutrophil count < 1.5 × 10^9/L. c) Platelet count < 100 × 10^9/L. d) Hemoglobin < 90 g/L. e) Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) > 2.5 × the upper limit of normal.
Pregnant or breastfeeding women.
Any serious or uncontrolled systemic disease, including uncontrolled hypertension, active bleeding, active infection (including hepatitis B, hepatitis C, HIV, etc.), which the investigator deems unsuitable for participation in the study or likely to affect compliance with the study protocol.
Trial design
Design model
Parallel
Treatments tested in this trial
circulating tumor DNA (ctDNA)-based MRD
Diagnostic testMRD testing will be performed before the start of the first treatment cycle, and at weeks 8 and 11 of each subsequent cycle. MinerVa Prime is a tumor-informed MRD assay based on a fixed panel spanning 769 cancer-related genes.
adjuvant chemotherapy regimens
DrugPatients will be administered with appropriate adjuvant chemotherapy regimens including but are not limited to: GEM monotherapy/adjustable GEM monotherapy, S-1 monotherapy/adjustable S-1 monotherapy, fluorouracil monotherapy/adjustable fluorouracil monotherapy, GEM plus CAP regimen/adjustable GEM plus CAP regimen, mFOLFIRINOX regimen, GEM plus nab-paclitaxel regimen/adjustable GEM plus nab-paclitaxel regimen.
Treatment groups
856 Participants
are divided into 2 treatment groupsGroup A: Arm A: MRD-guided adjuvant treatmentExperimental treatment 2 interventions
Group B: Arm B: non-MRD-driven, standard of care adjuvant treatmentPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Disease free survival (DFS)
To evaluate the impact of ct-DNA MRD-guided adjuvant therapy on disease-free survival (DFS), defined as the proportion of patients alive without objectively documented disease progression from the time of randomization until the 36th month.
Time frame
From the time of randomization up to three yearsSecondary outcomes
1
Overall survival (OS)
To evaluate the impact of ct-DNA MRD-guided adjuvant therapy on overall survival (OS), defined as the proportion of patients alive from the time of randomization until the 36th month (3-year OS rate) or until the 60th month(5-years OS rate).
Time frame
From the time of randomization until the 36th month (3-year OS rate) or until the 60th month(5-years OS rate)2
Adjuvant chemotherapy completion rate
Adjuvant chemotherapy completion rate, defined in the experimental group (arm A) as the proportion of patients completing 1-cycle, 2-cycle, 3-cycle, or 4-cycle treatment based on MRD results (each cycle is about 12 weeks), and in the control group (arm B) as the proportion of patients completing the prescribed chemotherapy duration (generally 2-cycle treatment, about 24 weeks).
Time frame
From the time of randomization to the end of treatment (arm A: 12 weeks, 24 weeks, 36 weeks, or 48 weeks; arm B: 24 weeks)3
Adverse events (AE) and serious adverse events (SAE) rates
Incidence of AE and SAE assessed via NCI CTCAE version 5.0 in the two treatment modalities. Definition of AE Possible adverse events include: drug-related peripheral sensory neuropathy, diarrhea, neutropenia, thrombocytopenia, nausea, vomiting, mucositis, fatigue, and hand-foot syndrome; as well as puncture site infections related to blood draws during the trial. Definition of SAE Possible serious adverse events include: 1. Death of the patient; 2. Life-threatening adverse events, such as Grade 4 non-hematologic toxicity or Grade 4 hematologic toxicity accompanied by fever and bleeding; 3. Any adverse event requiring hospitalization or prolongation of existing hospitalization; 4. Irreversible adverse events; 5. Unexpected adverse events not listed in the drug label that may impact the continuation of the study.
Time frame
From the time of randomization until the date of first recorded adverse events or serious adverse events as mentioned above, assessed up to 60 months (5-years)Sponsors and contacts
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Ruijin Hospital
Lead sponsor
GeneCast Biotechnology Co., Ltd.
Collaborator
Source ClinicalTrials.gov