Adjuvant Pancreatic Therapy Guided by MRD

NCT06966440 | Recruiting

• 1 other identifier: S-C2504015-PC
• Study Type: interventional
• Target: 856
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pancreatic Adenocarcinoma Resectable

Outcome Measures

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.

  From the time of randomization up to three years

Secondary Outcomes (3)

• Overall survival (OS)

  From the time of randomization until the 36th month (3-year OS rate) or until the 60th month(5-years OS rate)

• Adjuvant chemotherapy completion rate

  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)

• Adverse events (AE) and serious adverse events (SAE) rates

  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)

Study Arms (2)

Arm A: MRD-guided adjuvant treatment

EXPERIMENTAL

In the experimental group, patients will receive a guideline-recommended adjuvant therapy regimen chosen by their physician, with each treatment cycle lasting 12 weeks. MRD testing will be performed before the start of the first treatment cycle, and at weeks 8 and 11 after the start of treatment. If two consecutive MRD tests after the start of treatment are negative, treatment will be discontinued, and the patient will undergo regular follow-up only. Otherwise, another treatment cycle will be added. Starting from the second cycle, MRD testing will only be performed at weeks 8 and 11 of each cycle. If two consecutive MRD tests are negative, treatment will be discontinued, and the patient will undergo regular follow-up (every 8 weeks). Otherwise, treatment cycles will continue until disease progression, patient intolerance to treatment, or study termination.

Diagnostic Test: circulating tumor DNA (ctDNA)-based MRD; Drug: adjuvant chemotherapy regimens

Arm B: non-MRD-driven, standard of care adjuvant treatment

PLACEBO COMPARATOR

The control group will receive standard post-operative adjuvant therapy (according to CSCO guideline-recommended treatment duration, generally 6 months) followed by regular follow-up (every 8 weeks).

Drug: adjuvant chemotherapy regimens

Interventions

circulating tumor DNA (ctDNA)-based MRD DIAGNOSTIC_TEST

MRD 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.

Also known as: MinerVa

Arm A: MRD-guided adjuvant treatment

adjuvant chemotherapy regimens DRUG

Patients 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.

Arm A: MRD-guided adjuvant treatment; Arm B: non-MRD-driven, standard of care adjuvant treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• ECOG PS 0-2.
• Fully recovered from surgery and able to receive adjuvant chemotherapy.
• Availability of sufficient tumor tissue for MRD testing.
• Patients with reproductive potential (female patients: must have entered the study after the menstrual period and with a negative pregnancy test) must agree to use two medically acceptable methods of contraception (one used by the patient and one by their partner) during the study and for 4 months (for females) or 6 months (for males) after the last study treatment.

You may not qualify if:

• 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.
• Concurrent presence of another malignancy or a history of malignancy (except for adequately treated carcinoma in situ of the cervix, basal cell carcinoma, or squamous cell carcinoma of the skin)
• Other conditions that the investigator deems unsuitable for participation in the study.

Sponsors & Collaborators

• Ruijin Hospital: lead
• GeneCast Biotechnology Co., Ltd.: collaborator

Study Sites (1)

Ruijing Hospital

Shanghai, China

RECRUITING

Related Publications (2)

• Xia L, Pu Q, Kang R, Mei J, Li L, Yang Y, Deng S, Feng G, Deng Y, Gan F, Lin Y, Ma L, Lin F, Yuan Y, Hu Y, Guo C, Liao H, Liu C, Zhu Y, Wang W, Liu Z, Xu Y, Li K, Li C, Chen W, Li Q, Du B, Zhang X, Kou Y, Wang Y, Wu Z, Che G, Chen Y, Shen S, Chen L, Xie D, Liu L. Dynamic ctDNA informs whole-course postoperative precise management of NSCLC (LUNGCA study). J Natl Cancer Inst. 2025 Jul 1;117(7):1474-1484. doi: 10.1093/jnci/djaf061.

  PMID: 40131728 BACKGROUND

• Xia L, Mei J, Kang R, Deng S, Chen Y, Yang Y, Feng G, Deng Y, Gan F, Lin Y, Pu Q, Ma L, Lin F, Yuan Y, Hu Y, Guo C, Liao H, Liu C, Zhu Y, Wang W, Liu Z, Xu Y, Li K, Li C, Li Q, He J, Chen W, Zhang X, Kou Y, Wang Y, Wu Z, Che G, Chen L, Liu L. Perioperative ctDNA-Based Molecular Residual Disease Detection for Non-Small Cell Lung Cancer: A Prospective Multicenter Cohort Study (LUNGCA-1). Clin Cancer Res. 2022 Aug 2;28(15):3308-3317. doi: 10.1158/1078-0432.CCR-21-3044.

  PMID: 34844976 BACKGROUND

Central Study Contacts

Baiyong Shen, Dr

CONTACT

008613901943778; shenby@shsmu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The adjuvant chemotherapy regimens in this study include, 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: April 21, 2025
• First Posted: May 11, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2030
• Last Updated: July 15, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)