Adjuvant Pancreatic Therapy Guided by MRD

NCT ID: NCT06966440

Last Updated: 2025-07-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 856 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-01
• Study Completion Date: 2030-06-01

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.

Detailed Description

In pancreatic cancer, circulating tumor DNA (ctDNA) carries tumor-specific mutations (e.g., KRAS, TP53), which can be tracked using next-generation sequencing (NGS) technology to detect minimal residual disease (MRD) after surgery. Previous observational studies suggest that ctDNA-positive patients have a significantly higher risk of postoperative recurrence. In the MRD window (2-12 weeks post-surgery), the median disease-free survival (DFS) for ctDNA-positive patients was only 6.37 months, compared to 33.31 months for ctDNA-negative patients (HR=5.45), indicating that ctDNA-positive patients may require intensified treatment. Furthermore, patients with persistent ctDNA positivity after completing adjuvant chemotherapy (e.g., gemcitabine) still have a high recurrence rate (70%-90%), suggesting the need for alternative treatment strategies.

In a previous study (NCT05479708) evaluating postoperative MRD detection using plasma ctDNA to assess survival benefits and optimize adjuvant chemotherapy strategies in resectable pancreatic cancer patients, we found that MRD-positive patients at 4-8 weeks post-surgery (Landmark MRD) had a higher risk of recurrence. Analysis from Landmark MRD to 36 weeks post-treatment showed that patients who converted from positive to negative MRD status (MRD clearance) had a significantly lower risk of recurrence compared to those who remained positive and those who converted from negative to positive, and MRD clearance was associated with significantly improved overall survival (OS).

Given the significant trauma of pancreatic surgery and the often poor postoperative physical condition of patients, the optimal adjuvant chemotherapy regimen (single-agent/combination, duration, initiation time, etc.) that balances patient recovery and recurrence control remains unclear. Serum biomarker CA 19-9 is commonly used to assess prognosis in pancreatic cancer but is not a reliable predictor of adjuvant therapy efficacy. Imaging methods such as CT/MRI are often used to assess residual tumor or recurrence risk, but their sensitivity and specificity are limited, making it difficult to accurately evaluate real-time tumor burden. Therefore, we designed a prospective, randomized, interventional clinical trial based on ctDNA MRD to guide adjuvant chemotherapy decisions in patients with radically resected pancreatic cancer. The aim is to evaluate whether a ctDNA-guided treatment approach can reduce the use of adjuvant chemotherapy in low-risk patients without increasing recurrence risk, while intensifying treatment in high-risk patients to improve prognosis.

A ctDNA MRD-guided adjuvant therapy approach can allow patients to receive individualized adjuvant treatment. When ctDNA MRD test results are negative, adjuvant chemotherapy can be stopped with active follow-up. This can ensure that clinical benefits are not compromised while avoiding unnecessary chemotherapy. In cases where ctDNA MRD remains positive, continuing treatment can provide patients with more intensive therapy and potentially lead to better prognoses.

Conditions

Pancreatic Adenocarcinoma Resectable

Study Design

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

Study Groups

Arm A: MRD-guided adjuvant treatment

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.

Group Type: EXPERIMENTAL

circulating tumor DNA (ctDNA)-based MRD

Intervention Type: 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.

adjuvant chemotherapy regimens

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

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).

Group Type: PLACEBO_COMPARATOR

adjuvant chemotherapy regimens

Intervention Type: 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.

Interventions

circulating tumor DNA (ctDNA)-based MRD

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.

Intervention Type: DIAGNOSTIC_TEST

adjuvant chemotherapy regimens

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.

Intervention Type: DRUG

Other Intervention Names

MinerVa

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GeneCast Biotechnology Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Ruijin Hospital

OTHER

Sponsor Role: lead

Responsible Party

BAIYONG SHEN

Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Ruijing Hospital

Shanghai, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Baiyong Shen, Dr

Role: CONTACT

shenby@shsmu.edu.cn

008613901943778

Facility Contacts

Baiyong Shen, Dr

Role: primary

shenby@shsmu.edu.cn

13901943778

References

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.

Reference Type: BACKGROUND

PMID: 40131728 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34844976 (View on PubMed)

Other Identifiers

S-C2504015-PC

Identifier Type: -

Identifier Source: org_study_id