Organoid-Guided Adjuvant Chemotherapy for Pancreatic Cancer

A Prospective, Randomized, Controlled Trial of Adjuvant Chemotherapy for Pancreatic Cancer Based on Organoid Drug Sensitivity Test

The purpose of this study is to explore whether adjuvant chemotherapy regimens guided by organoid drug sensitivity test can improve the outcomes of pancreatic cancer. At the same time, this study will evaluate the successful establishment rate of organoid from fresh surgical specimens , and explore the concordance between drug sensitivity test results and patients' treatment response.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Other: Adjuvant chemotherapy guided by organoid drug sensitivity test

Detailed Description

The poor prognosis of pancreatic cancer is not just because of the high malignancy of the tumor itself, but also its poor response to chemotherapy. At present, patient's drug-sensitivity is assessed by progression time after treatment. Therefore, it is difficult to judge a patient's sensitivity to a drug before adjuvant chemotherapy. Organoid is a new tumor model, which has the potential to test the drug sensitivity before chemotherapy.

Our center's previous experience has shown that the success rate of pancreatic cancer organoid culture is 77.6%. The previous research has confirmed that pancreatic cancer organoid was highly consistent with the original tissue in terms of genomics and histomorphology. More importantly, the investigators have tested the five first-line drug-sensitivity in 39 pancreatic cancer organoids, and compared the test results with the clinical treatment response of these patients, confirming that organoid can accurately evaluate the chemotherapy drug-sensitivity.

This is a single-center, prospective, open-label, randomized, controlled clinical trial, designed to explore whether adjuvant chemotherapy regimens guided by organoid drug sensitivity test can improve outcomes in pancreatic cancer patients. At the same time, the consistency between the drug sensitivity test results and the treatment response of patients will be analyzed. Also, the radiosensitivity of organoid will be tested, and be compared with the patients' response to radiotherapy.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Shiwei Guo, M.D.; Phone Number: +8618621500666; Email: gestwa@163.com
• Study Contact Backup: Name: Huan Wang, Master; Phone Number: +8617317492841; Email: mr_wang_huan@163.com

Study Locations

• China
  • Shanghai, China, 200433
    • Recruiting
    • Changhai Hospital
    • Contact: Shiwei Guo, M.D.; Phone Number: +8618621500666; Email: gestwa@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age≥18 years old and ≤80 years old.
• Complete R0 resection for pancreatic cancer with no evidence of malignant ascites, peritoneal metastases or distant metastases.
• Histology confirmed pancreatic adenocarcinoma.
• Eligible histologic variants include adenocarcinoma or variants to include mucinous adenocarcinoma or adenosquamous carcinoma.
• No metastases are found in preoperative examination.
• No prior chemotherapy or radiotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of greater than 90 days, as judged by the investigator.
• Routine blood test: absolute neutrophil count>1500/mm3, platelet>100000/mm3.
• Normal liver function: serum total bilirubin≤2.0mg/dl, aminotransferase (ALT) and aspertate aminotransferase (AST) <2.5 times of the upper limit of normal value.
• Normal kidney function: serum creatinine<1.5 times of the upper limit of normal value or creatinine clearance rate>45ml/min.
• The pancreatic cancer organoid were cultured successfully.
• No severe comorbidities.

Exclusion Criteria:

• Patients with poor condition can not tolerate chemotherapy and targeted therapy.
• Impaired organ functions: heart failure (New York Heart Association III-IV), coronary heart disease, myocardial infarction within 6 months, severe cardiac arrhythmia and respiratory failure.
• Patients diagnosed with other cancer within 5 years.
• Patients who are pregnant or breastfeeding.
• Patients enrolled in other clinical trials or incompliant of regular follow up.
• Patients who did not provide an informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Organoid-Guided Adjuvant Chemotherapy; The pancreatic cancer specimens are obtained from surgery to be cultured for organoids. Then drug sensitivity is tested using organoid to obtain the sensitivity to the first-line drugs for pancreatic cancer (Gemcitabine, 5-fluorouracil, Paclitaxel, Oxaliplatin, Irinotecan). Patients will receive relatively sensitive chemotherapy regimen based on the test results. Adjuvant chemotherapy should start within 2 months after surgery, and last at least 6 months.	Other: Adjuvant chemotherapy guided by organoid drug sensitivity test; Adjuvant chemotherapy guided by organoid will be given to pancreatic cancer patients.
NO_INTERVENTION: Physician-decided Adjuvant Chemotherapy; The pancreatic cancer specimens are obtained from surgery to be cultured for organoids. Then drug sensitivity is tested using organoid to obtain the sensitivity to the first-line drugs for pancreatic cancer (Gemcitabine, 5-fluorouracil, Paclitaxel, Oxaliplatin, Irinotecan). Physician will decide the the adjuvant chemotherapy regimen, according to National Comprehensive Cancer Network (NCCN) guideline for pancreatic ductal adenocarcinoma. And they don't know the drug sensitivity test results. Adjuvant chemotherapy should start within 2 months after surgery, and last at least 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease free time	Time from the date of randomization to recurrence based on the radiology assessment of response using RECIST v1.1, or death, whichever is earlier.	1-2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival time	The time from the date of randomization to the date of death for any cause. Patients will be followed until their date of death or until final database closure. Patients who are lost-to-follow-up or are alive at the time of analysis will be censored at the time they were last known to be alive or at the date of event cut-off for Overall survival (OS) analysis.	2-4 years
1-year disease-free survival	The percentage of patients without recurrence by one year.	1 year
The successful establishment rate of organoids	The rate of organoid successfully cultured in all the samples collected.	2-4 years
Concordance between drug sensitivity test results and patients' treatment response (descriptive statistics).	To assess the accuracy of drug sensitivity test in both group.The number of patients with correct prediction of treatment response by organoid drug-sensitivity test divided by the number of patients underwent chemotherapy.	2-4 years
Concordance between radiosensitivity test results and patients' treatment response (descriptive statistics).	To assess the accuracy of radiosensitivity test in both group. The number of patients with correct prediction of treatment response by organoid radiosensitivity test divided by the number of patients underwent radiotherapy.	2-4 years

Collaborators and Investigators

• Sponsor: Changhai Hospital
• Investigators: Principal Investigator: Gang Jin, M.D., Changhai hospital, Shanghai, China

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2021
• Primary Completion (ANTICIPATED): May 31, 2024
• Study Completion (ANTICIPATED): May 31, 2025

Study Registration Dates

• First Submitted: June 15, 2021
• First Submitted That Met QC Criteria: June 15, 2021
• First Posted (ACTUAL): June 18, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 2, 2022
• Last Update Submitted That Met QC Criteria: July 29, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Pancreatic Cancer; Chemotherapy; Organoid; Drug Sensitivity Test
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: ChanghaiH-PP08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No