3D Bioprinted Models for Predicting Chemotherapy Response in Colorectal Cancer With/Without Liver Metastases

Validation of the Three-dimensional Bioprinted Tumor Models as a Predictive Method of the Response to Chemotherapy for Colorectal Cancer With or Without Liver Metastases

The therapeutic regimens of adjuvant and neoadjuvant chemotherapy for colorectal cancer (CRC) remain largely relied on clinical experience, and thus preclinical models are needed to guide individualized medicine. The investigators are going to establish 3D bioprinted CRC models and organoids from surgically resected tumor tissues of CRC patients with or without liver metastases. In vitro 3D models and organoids will be treated with the same chemotherapy drugs with the corresponding patients from whom the models are derived. The sensitivity of chemotherapy drugs will be tested in these two types of in vitro models, and the actual response to chemotherapy in patients will be evaluated. The predictive ability of 3D models for chemotherapy sensitivity in CRC patients will be compared with that of the organoids. This observational study will validate the potential value of 3D bioprinted tumor models in predicting the response to chemotherapy in CRC.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Colorectal Cancer Liver Metastasis
• Intervention / Treatment: Procedure: surgical resection; Other: adjuvant chemotherapy; Other: neoadjuvant therapy

• Study Type: Observational
• Enrollment (Anticipated): 120

Contacts and Locations

• Study Contact: Name: Yilei Mao, MD PhD; Phone Number: 8600-010-69156042; Email: pumch-liver@hotmail.com
• Study Contact Backup: Name: Lejia Sun, MD; Phone Number: 8600-18811152352; Email: sunlejia361@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Yilei Mao, MD PhD; Phone Number: 8600-010-69156042; Email: pumch-liver@hotmail.com
      • Contact: Lejia Sun, MD; Phone Number: 8600-18811152352; Email: sunlejia361@163.com
    • Beijing, Beijing, China, 100143
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Baocai Xing, MD; Phone Number: 8600-010-88196098; Email: xingbaocai88@sina.com
    • Beijing, Beijing, China, 100029
      • Recruiting
      • China-Japan Friendship Hospital
      • Contact: Zhiying Yang, MD; Phone Number: 8600-010-84205017; Email: yangzhy@aliyun.com
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Cancer Institute and Hospital, Chinese Academy of Medical Sciences
      • Contact: Hong Zhao, MD; Phone Number: 8600-010-87787100; Email: zhaohong@cicams.ac.cn

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Clinically and pathologically proven colorectal cancer patients are considered as potential candidates of this study. Medical history will be thouroughly taken by clincal practicitioners. Only patients older than 18 years will be included. Those with medical hostory of other malignancies or serious diseases will be excluded. Patients who are not able to sign the informed consent independently will not be included in this study. All the patients included in this study will receive adjuvant/neoadjuvant chemotherapy and surgical resection for the treatment of CRC.

Description

Inclusion Criteria:

• More than 18 years old
• Diagnosed as colorectal cancer with or without liver metastases before
• Pathologically proven colorectal cancer after surgery

Exclusion Criteria:

• Medical history with other malignancies or serious diseases
• Disable to sign the informed consent independently

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group A; colorectal cancer patients at resectable stage II/III who will receive adjuvant chemotherapy after surgery	Procedure: surgical resection; Surgical resection will be performed for locoregional lesions or liver metastases.; Other: adjuvant chemotherapy; Regimens of adjuvant chemotherapy are directed by clinical guidance and experience.
Group B; colorectal cancer patients at locally advanced stage who will receive neoadjuvant chemotherapy before surgery and adjuvant chemotherapy after surgery	Procedure: surgical resection; Surgical resection will be performed for locoregional lesions or liver metastases.; Other: adjuvant chemotherapy; Regimens of adjuvant chemotherapy are directed by clinical guidance and experience.; Other: neoadjuvant therapy; Regimens of neoadjuvant chemotherapy are directed by clinical guidance and experience.
Group C; colorectal cancer patients with liver metastases	Procedure: surgical resection; Surgical resection will be performed for locoregional lesions or liver metastases.; Other: adjuvant chemotherapy; Regimens of adjuvant chemotherapy are directed by clinical guidance and experience.; Other: neoadjuvant therapy; Regimens of neoadjuvant chemotherapy are directed by clinical guidance and experience.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response of 3D tumor models/organoids to the same chemotherapy drugs as the corresponding patients.	The investigators will establish and culture 3D colorectal cancer models and organoids. The 3D models and organoids will be treated with the same chemotherapy drugs as the corresponding patients. The viability of the 3D tumor models and organoids will be observed after treatment and the IC50 of each drug will be calculated. The correlation of 3D model/organoid sensitivity and the patient response will be analyzed.	2021.03-2021.12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response of the colorectal cancer patients to neoadjuvant chemotherapy.	For patients who receive neoadjuvant chemotherapy before surgery, the response to neoadjuvant chemotherapy will be evaluated according to clinical imaging results and the RECIST scores.	2021.03-2022.03

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response of the colorectal cancer patients to adjuvant chemotherapy.	The response to adjuvant chemotherapy will be evaluated according to disease free survival (DFS). Regular follow-ups will be conducted, and DFS is difined as the interval between the date of surgery and the date of last follow-up or recurrence/progression.	2021.03-2023.12

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Peking University Cancer Hospital & Institute; China-Japan Friendship Hospital
• Investigators: Principal Investigator: Yilei Mao, MD PhD, Peking Union Medical College Hospital

Publications and helpful links

General Publications

• Bruun J, Kryeziu K, Eide PW, Moosavi SH, Eilertsen IA, Langerud J, Rosok B, Totland MZ, Brunsell TH, Pellinen T, Saarela J, Bergsland CH, Palmer HG, Brudvik KW, Guren T, Dienstmann R, Guren MG, Nesbakken A, Bjornbeth BA, Sveen A, Lothe RA. Patient-Derived Organoids from Multiple Colorectal Cancer Liver Metastases Reveal Moderate Intra-patient Pharmacotranscriptomic Heterogeneity. Clin Cancer Res. 2020 Aug 1;26(15):4107-4119. doi: 10.1158/1078-0432.CCR-19-3637. Epub 2020 Apr 16.
• Wu J, Lu AD, Zhang LP, Zuo YX, Jia YP. [Study of clinical outcome and prognosis in pediatric core binding factor-acute myeloid leukemia]. Zhonghua Xue Ye Xue Za Zhi. 2019 Jan 14;40(1):52-57. doi: 10.3760/cma.j.issn.0253-2727.2019.01.010. Chinese.
• Brancato V, Oliveira JM, Correlo VM, Reis RL, Kundu SC. Could 3D models of cancer enhance drug screening? Biomaterials. 2020 Feb;232:119744. doi: 10.1016/j.biomaterials.2019.119744. Epub 2019 Dec 26.
• Yao Y, Xu X, Yang L, Zhu J, Wan J, Shen L, Xia F, Fu G, Deng Y, Pan M, Guo Q, Gao X, Li Y, Rao X, Zhou Y, Liang L, Wang Y, Zhang J, Zhang H, Li G, Zhang L, Peng J, Cai S, Hu C, Gao J, Clevers H, Zhang Z, Hua G. Patient-Derived Organoids Predict Chemoradiation Responses of Locally Advanced Rectal Cancer. Cell Stem Cell. 2020 Jan 2;26(1):17-26.e6. doi: 10.1016/j.stem.2019.10.010. Epub 2019 Nov 21.
• Xie F, Sun L, Pang Y, Xu G, Jin B, Xu H, Lu X, Xu Y, Du S, Wang Y, Feng S, Sang X, Zhong S, Wang X, Sun W, Zhao H, Zhang H, Yang H, Huang P, Mao Y. Three-dimensional bio-printing of primary human hepatocellular carcinoma for personalized medicine. Biomaterials. 2021 Jan;265:120416. doi: 10.1016/j.biomaterials.2020.120416. Epub 2020 Sep 22.
• Sun L, Yang H, Wang Y, Zhang X, Jin B, Xie F, Jin Y, Pang Y, Zhao H, Lu X, Sang X, Zhang H, Lin F, Sun W, Huang P, Mao Y. Application of a 3D Bioprinted Hepatocellular Carcinoma Cell Model in Antitumor Drug Research. Front Oncol. 2020 Jun 3;10:878. doi: 10.3389/fonc.2020.00878. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2021
• Primary Completion (ANTICIPATED): December 31, 2022
• Study Completion (ANTICIPATED): December 31, 2023

Study Registration Dates

• First Submitted: February 13, 2021
• First Submitted That Met QC Criteria: February 13, 2021
• First Posted (ACTUAL): February 16, 2021

Study Record Updates

• Last Update Posted (ACTUAL): July 19, 2022
• Last Update Submitted That Met QC Criteria: July 16, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: colorectal cancer; chemotherapy; colorectal cancer liver metastasis; three-dimensional bioprinting
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Liver Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis; Liver Neoplasms
• Other Study ID Numbers: CRC-3D-Bioprint

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) can be accessed with reasonable requests via e-mail. IPD will be shared after the study is completed.
• IPD Sharing Time Frame: The IPD data will available after the study is completed.
• IPD Sharing Access Criteria: Data can be accessed via e-mail with reasonable requests.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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