Cetuximab Sensitivity Correlation Between Patient-Derived Organoids and Clinical Response in Colon Cancer Patients.

Patient-derived Organoids of RAS/RAF Wild-type Metastatic Right Colon Cancer to Test the Sensitivity and Clinical Consistency of Combined Treatment of Cetuximab.

Eighty patients with RAS/RAF wild-type metastatic right colon cancer will be enrolled and undergo a fresh biopsy of tumor lesion before the standard treatment of chemotherapy. The investigators will establish organoids from the pre-treatment biopsies. Organoids will be exposed to the chemotherapy drugs or chemotherapy drugs combined with cetuximab used for each patient. The sensitivity of chemotherapy drugs or combined cetuximab will be tested in the organoids model. Chemotherapy strategies including 5-fluorouracil only, irinotecan only, oxaliplatin only, FOLFOX, and FOLFIRI. The purpose of this study is to evaluate the consistency and accuracy of a Patient-Derived Organoid (PDO) model of colon cancer to predict the clinical efficacy of combined treatment of cetuximab, which to formulate the best therapy regimen for each given patient.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Cancer; Colon Cancer; Organoids
• Intervention / Treatment: Procedure: Tumor biopsy

Detailed Description

Investigators hypothesize that the cetuximab sensitivity test results on patient-derived organoids can be used to predict the treatment selection of patients with RAS/RAF wild-type metastatic right colon cancer.

Objectives

1. To assess the effective rate of cetuximab target therapy on RAS/RAF wild-type right colon cancer
2. To assess the consistency of organoid chemotherapy sensitivity and clinical chemotherapy efficacy
3. To assess the consistency of organoid cetuximab sensitivity and clinical cetuximab efficacy

The following points will be addressed:

1. The biopsy tissue of RAS/RAF wild-type metastatic right colon cancer will be collected and subject to ex vivo 3-D culture to establish patient-derived tumor organoids, which will be used for the drug sensitivity test.
2. Enrolled patients will treat with chemotherapy or chemotherapy combined target therapy. The medication regime and treatment cycle will be decided based on the clinical guideline and evidence-based medicine.
3. The patient-derived organoid-based drug sensitivity test will compare with clinical treatment data of chemotherapy or chemotherapy combined target therapy, followed by correlation analysis.

• Study Type: Observational
• Enrollment (Anticipated): 80

Contacts and Locations

• Study Contact: Name: Hanqing Lin, Dr.; Phone Number: +8615921348040; Email: linhq@d1med.com
• Study Contact Backup: Name: Chunyan Cheng, Dr.; Phone Number: +8613916290275; Email: chengcy@d1med.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Junjie Peng, Dr.; Phone Number: +8602164175590; Email: pengjj67@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The Department of Colorectal Surgery in Fudan University Cancer Hospital is one of the largest colorectal cancer diagnosis and treatment centers in China. In 2019, more than 1,000 cases of recurrent and metastatic colorectal cancer were diagnosed and treated. It is sufficient to obtain samples for this study from patients diagnosed and treated in this department.

Description

Inclusion Criteria:

1. Age from 18 to 70 years old, no gender limit
2. The primary tumor is located in the right colon, including the ileocecal area, ascending colon, liver flexure, and the right part of the transverse colon.
3. Pathologically proved primary intestinal tumor with simultaneous / metachronous metastasis
4. Molecular pathology confirmed as RAS/RAF wild type
5. Can tolerate and cooperate with the completion of chemotherapy and targeted therapy
6. Tissues can be obtained through puncture or colonoscopy for organoid culture
7. Complete clinical data, as well as efficacy evaluation data, can be obtained

Exclusion Criteria:

1. Less than 18 years of age or more than 70 years of age
2. The primary tumor is located in the left colon or rectum
3. Pathology results can't confirm as colon cancer
4. RAS and RAF are mutant confirmed by molecular pathology
5. Refuse to cooperate and complete the treatment, or there is a contraindication for chemotherapy or targeted therapy
6. No available metastatic lesions tissue
7. Unable to obtain complete clinical data or efficacy evaluation data

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cancer patient; RAS/RAF wild-type metastatic right colon cancer patients receiving chemotherapy or chemotherapy combined target therapy treatment.	Procedure: Tumor biopsy; Patients with RAS/RAF wild-type metastatic right colon cancer will receive biopsy before the standard treatment of chemotherapy or target therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of ex vivo sensitivity test on patient-derived organoid models with clinical outcomes	The drug sensitivity tests on patient-derived tumor organoids will compare with the clinical response of the chemo- or targeted therapy treatment. The correlation of organoids sensitivity and patient response will be evaluated.	2021.05-2023.05

Collaborators and Investigators

• Sponsor: D1 Medical Technology (Shanghai) Co., Ltd, China
• Collaborators: Fudan University
• Investigators: Principal Investigator: Junjie Peng, Dr., Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2021
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: May 27, 2021
• First Submitted That Met QC Criteria: May 27, 2021
• First Posted (Actual): May 28, 2021

Study Record Updates

• Last Update Posted (Actual): August 13, 2021
• Last Update Submitted That Met QC Criteria: August 11, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms
• Other Study ID Numbers: D1med-ZL01

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
• product manufactured in and exported from the U.S.: Yes