Immune Checkpoints in Colorectal Cancer

Colorectal Cancer Clinical Trial

Official title:

Immune Checkpoints in Colorectal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04051450
• Other study ID #: CRC_immune2018
• Status: Recruiting
• Start date: May 1, 2020
• Est. completion date: May 1, 2024

Study information

• Verified date: February 2021
• Source: Chinese University of Hong Kong
• Contact: ST Cheung, PhD
• Phone: 852 35051121
• Email: stcheung[@]surgery.cuhk.edu.hk
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Colorectal cancer (CRC) ranked the first in cancer incidence in Hong Kong and it is frequently lethal with heterogeneous drug responses and survival outcomes. Immune-based approaches targeting to enhance tumor-specific responses have been actively under investigation as therapeutic strategies. Currently, PD1 and PD-L1 blockade has shown promising results in clinical trials especially in colorectal cancer patients with microsatellite instability. This study aims to examine the role of PD-L1/PD1 in immune cell-mediated cytotoxicity in colorectal cancer patients.

Description:

Aim: To examine the role of PD-L1/PD1 in immune cell-mediated cytotoxicity in colorectal cancer patients. Objectives: 1. Comprehensive investigation of PD-L1/PD1 in colorectal cancer in association with chemotherapy responses and immune activities; 2. Examine the functional role of PD-L1/PD1 targeting in immune cell-mediated cytotoxicity. Hypothesis: It is hypothesized that PD-L1/PD1 has pivotal role on the immune cell-mediated cytotoxicity in colorectal cancer. Significances: The current study will elucidate the significance of PD-L1/PD1 on chemo-resistance and the effect on immune cells and their functional properties. The study will enhance the understanding on chemotherapy response and immune evasion. The long-term goal is to provide the crucial information on oncoimmunology to improve efficacy of immunotherapy in cancer treatment. Subjects: Only those patients for whom colorectal cancer is the indicated clinical diagnosis will be recruited in the current study. Possible participants will be patients undergoing tumor resection or endoscopic examination at the Department of Surgery, Prince of Wales Hospital, Shatin, Hong Kong. Specimens will be collected from sixty-eight colorectal cancer patients. The estimated duration for collection of all the necessary samples will be two years. With at least one year of follow-up information, the proposed study should be completed in three years. For the current study, single blood sample (10 ml of peripheral blood in EDTA) will be drawn before the operation or endoscopic session. A small portion of the tumor and non-tumor tissue tissues from resected specimens or biopsy tissues will be collected for histological evaluation, primary culture and for comparison of the genetic and protein components in the blood specimen.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 68
• Est. completion date: May 1, 2024
• Est. primary completion date: May 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• colorectal cancer patients undergoing resection or endoscopic examination at the Department of Surgery, Prince of Wales Hospital, Shatin, Hong Kong

Exclusion Criteria:

• patients who do not consent

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Locations

Country	Name	City	State
Hong Kong	The Chinese University of Hong Kong	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
Chinese University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

References & Publications (5)

Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2014 Apr 26;383(9927):1490-1502. doi: 10.1016/S0140-6736(13)61649-9. Epub 2013 Nov 11. Review. — View Citation

Farkona S, Diamandis EP, Blasutig IM. Cancer immunotherapy: the beginning of the end of cancer? BMC Med. 2016 May 5;14:73. doi: 10.1186/s12916-016-0623-5. Review. — View Citation

Guinney J, Dienstmann R, Wang X, de Reyniès A, Schlicker A, Soneson C, Marisa L, Roepman P, Nyamundanda G, Angelino P, Bot BM, Morris JS, Simon IM, Gerster S, Fessler E, De Sousa E Melo F, Missiaglia E, Ramay H, Barras D, Homicsko K, Maru D, Manyam GC, Broom B, Boige V, Perez-Villamil B, Laderas T, Salazar R, Gray JW, Hanahan D, Tabernero J, Bernards R, Friend SH, Laurent-Puig P, Medema JP, Sadanandam A, Wessels L, Delorenzi M, Kopetz S, Vermeulen L, Tejpar S. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015 Nov;21(11):1350-6. doi: 10.1038/nm.3967. Epub 2015 Oct 12. — View Citation

Llosa NJ, Cruise M, Tam A, Wicks EC, Hechenbleikner EM, Taube JM, Blosser RL, Fan H, Wang H, Luber BS, Zhang M, Papadopoulos N, Kinzler KW, Vogelstein B, Sears CL, Anders RA, Pardoll DM, Housseau F. The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov. 2015 Jan;5(1):43-51. doi: 10.1158/2159-8290.CD-14-0863. Epub 2014 Oct 30. — View Citation

Passardi A, Canale M, Valgiusti M, Ulivi P. Immune Checkpoints as a Target for Colorectal Cancer Treatment. Int J Mol Sci. 2017 Jun 21;18(6). pii: E1324. doi: 10.3390/ijms18061324. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Generation of candidate biomarkers PD-L1/PD1/GEP by laboratory assay qPCR for prognostication.	Biomarkers PD-L1/PD1/GEP will be investigated by laboratory assay real-time quantitative PCR. The biomarker levels in tissue specimens and the association with recurrence-free survival will be analyzed for prognostication.	Three years.