Study on Consistency Evaluation for Drug Sensitivity of Patient-Derived Organoid Model From Cholangiocarcinoma Patients

Clinical Study on the Drug Sensitivity Consistency of Patient-Derived Organoid Model and Actual Therapeutic Efficacies in Cholangiocarcinoma Patients Receiving Adjuvant Chemotherapy After Radical Resection

This is a single-center, prospective, observational and exploratory clinical study. The object of this study is to evaluate the consistency and accuracy of patient-derived organoid model of cholangiocarcinoma to predict the clinical chemotherapeutic efficacy, as well as the possibility of guiding the adjuvant chemotherapy.

Study Overview

• Status: Recruiting
• Conditions: Cholangiocarcinoma
• Intervention / Treatment: Other: No interventions.

Detailed Description

The chemotherapeutic efficacy is heterogeneous among cholangiocarcinoma patients after radical resection, and an accurate and relatively convenient model evaluating the chemotherapeutic efficacy is still lacking. This study aims to prospectively evaluate the consistency of drug sensitivity between patient-derived organoid model and the actual clinical chemotherapeutic efficacy in cholangiocarcinoma patients, assisting in guiding precision medicine and making therapeutic decisions.

Drug sensitivity tests include single drug and drug combination. The organoids that are successfully cultured will be kept in liquid nitrogen for a specific time.

• Study Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510220
      • Recruiting
      • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Histologically confirmed cholangiocarcinoma patients who underwent radical resection and received post-operation adjuvant chemotherapy.

Description

Inclusion Criteria:

1. The patient must sign an informed consent form;
2. Age 18-75 years old, both male and female;
3. ECOG performance status score (PS score) 0-2;
4. Child-Pugh score A period;
5. Cholangiocarcinoma with negative margins confirmed by histopathology;
6. Have not received any systemic treatment within 6 months;
7. The functional indicators of important organs meet the following requirements (1)Neutrophils≥1.5*109/L; platelets≥100*109/L; hemoglobin≥9g/dl; serum albumin≥3g/dl; (2)Thyroid-stimulating hormone (TSH) ≤ 2 times the upper limit of normal, and T3 and T4 are in the normal range; (3)Bilirubin ≤ 1.5 times the upper limit of normal; ALT and AST ≤ 3 times the upper limit of normal; (4)Serum creatinine ≤ 1.5 times the upper limit of normal, and creatinine clearance ≥ 60ml/min (calculated by Cockcroft-Gault formula);
8. For women who are not breastfeeding or pregnant, use contraception during treatment or 12 months after the end of treatment.

Exclusion Criteria:

1. Unresectable cholangiocarcinoma patients or postoperative diagnosis of cholangiocarcinoma recurrence and metastasis;
2. Past or simultaneous suffering from other malignant tumors;
3. Have used gemcitabine-based chemotherapy or radiotherapy within 6 months;
4. Severe cardiopulmonary and renal dysfunction;
5. Hypertension that is difficult to control with drugs (systolic blood pressure (BP) ≥140 mmHg and/or diastolic blood pressure ≥90mmHg) (based on the average of ≥3 BP readings obtained by ≥2 measurements);
6. Abnormal coagulation function (PT>14s), have bleeding tendency or are receiving thrombolysis or anticoagulation therapy;
7. After antiviral treatment, HBV DNA>2000 copies/ml, HCV RNA>1000;
8. A history of esophageal and gastric varices, significant clinically significant bleeding symptoms or a clear tendency to appear within 3 months before enrollment;
9. Active infections requiring systemic treatment; patients with active tuberculosis infection within 1 year before enrollment; a history of active tuberculosis infection more than 1 year before enrollment, and no formal anti-tuberculosis treatment or tuberculosis Still in the active period;
10. Human immunodeficiency virus (HIV, HIV1/2 antibody) positive;
11. A history of psychotropic drug abuse, alcohol or drug abuse;
12. Known to have a history of severe allergies to any platinum drugs, or gemcitabine;
13. Other factors judged by the investigator may affect the safety of the subjects or the compliance of the trial. Such as serious diseases (including mental illness) that require combined treatment, serious laboratory abnormalities, or other family or social factors.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Sun Yat-Sen Memorial Hospital of Sun Yat-sen University; The cohort of Sun Yat-Sen Memorial Hospital of Sun Yat-sen University is the exploration cohort.	Other: No interventions.; No interventions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival status of cholangiocarcinoma patients after radical resection	The cholangiocarcinoma patients after radical resection are regularly followed-up for the progression-free survival status.	12 months
Drug sensitivity of patient-derived tumor organoids	The drug sensitivity is tested on patient-derived tumor organoids, which is evaluated using Promega CellTiter-Glo 3D Cell Viability Assay to calculate the relative IC50, and is compared with the actual chemotherapeutic efficacy of cholangiocarcinoma patients.	2 months

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Anticipated): November 30, 2022
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: November 16, 2022
• First Submitted That Met QC Criteria: November 29, 2022
• First Posted (Actual): December 2, 2022

Study Record Updates

• Last Update Posted (Actual): December 2, 2022
• Last Update Submitted That Met QC Criteria: November 29, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Chemotherapy; Cholangiocarcinoma; Adjuvant therapy; Patient-Derived Organoid; Drug Sensitivity
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Hypersensitivity; Cholangiocarcinoma
• Other Study ID Numbers: SYSKY-2022-168-01

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