Molecular Study and Precision Medicine for Colorectal Cancer (MSPM)

Precision Medicine for Advanced or Recurrent Colorectal Cancer Directed by High-throughput Sequencing and Tumor Organoids Model

Researchers collect specimens from advanced or recurrent colorectal cancer (CRC) patients to conduct molecular profiling and establish tumor organoids (PDOs)/ patient-derived xenografts (PDXs). The aim of this study is to identify clinical actionable targets and predict in vivo response of the tumor to targeted drugs by using PDOs/ PDXs. And the above-mentioned studies will provide the patients with potential personalized cancer treatment options.

Study Overview

• Status: Not yet recruiting
• Conditions: Recurrent Colorectal Carcinoma; Advanced Colorectal Carcinoma
• Intervention / Treatment: Other: Molecular Profiling & drug testing in tumor organoids and PDXs

Detailed Description

Patient-derived organoid is a model that can recapitulate the histology and behavior of the cancer from which it is derived, and is increasingly used as a tool for drug development in pre-clinical settings. Clinical treatment option of colorectal cancer now is quite limited. By molecular profiling, clinical actionable alterations may be identified. And according to the genomic investigation results, we can find the matched targeted drugs, following further testing in the organoids and PDXs. This will provide an opportunity to guide the precision medicine.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Zheng Wang, MD/PhD; Phone Number: +86 2785726612; Email: zhengwang@hust.edu.cn
• Study Contact Backup: Name: Luming Xu; Phone Number: +86 2785726612; Email: lumingxu@hust.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Wuhan Union Hospital, China
      • Contact: Zheng Wang, MD/PhD; Phone Number: +86278576612

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

patients with advanced or recurrent colorectal cancer

Description

Inclusion Criteria:

• Male or female patients, age 18 to 75 years old
• Patients with a documented (histologically- or cytologically-proven) advanced or recurrent colorectal cancer
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1 and a life expectancy of at least 3 months
• Patients, both male and female, who are either not of childbearing potential or who agree to use a medically effective method of contraception during the study and for 3 months after the last dose of study drug.
• Patients with the ability to understand and give written informed consent for participation in this trial, including all evaluations and procedures as specified by this protocol.

Exclusion Criteria:

• Patients with any other life-threatening illness, significant organ system dysfunction, or clinically significant laboratory abnormality, which, in the opinion of the Investigator, would either compromise the patient's safety or interfere with evaluation of the safety of the study drug
• Patients with abnormal coagulation function, bleeding tendency, or receiving thrombolytic or anticoagulant therapy
• Patients with any other serious/active/uncontrolled infection, any infection requiring parenteral antibiotics, or unexplained fever > 38ºC within 2 weeks prior to first study drug administration.
• Patients with a history of human immunodeficiency virus (HIV) or any other immunodeficiency disease.
• Patients who are currently using certain drugs that are not permitted
• Patients with a psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary studies
• Patients with the inability, in the opinion of the Investigator, to comply with the protocol requirements

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Colorectal Cancer; Colorectal cancer patients with advanced or recurrent tumors

Other: Molecular Profiling & drug testing in tumor organoids and PDXs; Molecular profiling of native tumor will be performed and analyzed by using a self-designed panel. Tumor organoids will be cultured from fresh tumor tissues and patient-derived xenografts model will be established using the tumor organoids. Drugs will be tested in the two models. And the recommendation will be communicated to the clinicians.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of effective drugs or drug combinations	Viability of organoid is measured using CellTiter-Glo by quantifying ATP, which indicates the presence of metabolically active cells.	up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of clinical actionable alterations identified in native tumor and organoids.	Genomic gene mutation numbers are identified using the Next-Generation Sequencing (NGS).	Up to 3 years
Correlation between organoid and PDX drug sensitivities	Size of the tumor is measured to reflect the drug response.	Up to 3 years

Collaborators and Investigators

• Sponsor: Wuhan Union Hospital, China
• Investigators: Study Chair: Zheng Wang, MD/PhD, Wuhan Union Hospital, China

Publications and helpful links

General Publications

• Pauli C, Hopkins BD, Prandi D, Shaw R, Fedrizzi T, Sboner A, Sailer V, Augello M, Puca L, Rosati R, McNary TJ, Churakova Y, Cheung C, Triscott J, Pisapia D, Rao R, Mosquera JM, Robinson B, Faltas BM, Emerling BE, Gadi VK, Bernard B, Elemento O, Beltran H, Demichelis F, Kemp CJ, Grandori C, Cantley LC, Rubin MA. Personalized In Vitro and In Vivo Cancer Models to Guide Precision Medicine. Cancer Discov. 2017 May;7(5):462-477. doi: 10.1158/2159-8290.CD-16-1154. Epub 2017 Mar 22.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: July 12, 2022
• First Submitted That Met QC Criteria: May 30, 2023
• First Posted (Actual): June 1, 2023

Study Record Updates

• Last Update Posted (Actual): June 1, 2023
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Carcinoma; Colorectal Neoplasms
• Other Study ID Numbers: CIT-CoPT-R01

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