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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04755907
• Other study ID #: CRC-3D-Bioprint
• Status: Recruiting
• Start date: March 1, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: July 2022
• Source: Peking Union Medical College Hospital
• Contact: Yilei Mao, MD PhD
• Phone: 8600-010-69156042
• Email: pumch-liver[@]hotmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Cancer Liver Metastasis
• Colorectal Neoplasms
• Liver Neoplasms
• Neoplasm Metastasis
• Neoplasms, Second Primary

Intervention

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.
• neoadjuvant therapy
Regimens of neoadjuvant chemotherapy are directed by clinical guidance and experience.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Cancer Institute and Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing
China	China-Japan Friendship Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing

Sponsors (4)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital	Beijing Cancer Hospital, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, China-Japan Friendship Hospital

Country where clinical trial is conducted

China, 

References & Publications (6)

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. Review. — View Citation

Bruun J, Kryeziu K, Eide PW, Moosavi SH, Eilertsen IA, Langerud J, Røsok B, Totland MZ, Brunsell TH, Pellinen T, Saarela J, Bergsland CH, Palmer HG, Brudvik KW, Guren T, Dienstmann R, Guren MG, Nesbakken A, Bjørnbeth 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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	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