Exploration of Therapeutic Strategies for NeoRAS Wild-type Metastatic Colorectal Cancer Based on Circulating Tumor DNA

Colorectal Cancer Metastatic Clinical Trial

Official title:

Exploration of Therapeutic Strategies for NeoRAS Wild-type Metastatic Colorectal Cancer Based on Circulating Tumor DNA: an Open, Prospective, Phase II Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06440902
• Other study ID #: ctDNA-neoRASCRC
• Status: Recruiting
• Phase: Phase 2
• Start date: December 28, 2023
• Est. completion date: September 1, 2028

Study information

• Verified date: May 2024
• Source: Fudan University
• Contact: Junjie Peng, PhD
• Phone: +86 13917373312
• Email: pengjj[@]shca.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Following systemic therapy in metastatic colorectal cancer(mCRC),RAS (including KRAS, NRAS and HRAS gene) status may change from a mutant(MT) to a wild-type(WT),a phenomenon known as "NeoRAS WT"mCRC.NeoRAS WT can be detected by longitudinal circulating tumor DNA(ctDNA) analysis.Therefore, this prospective phase II Study was design to explore the detection rate of peripheral blood ctDNA testing for NeoRAS WT and its guiding value for subsequent treatment for mCRC.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1100
• Est. completion date: September 1, 2028
• Est. primary completion date: September 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Metastatic colorectal cancer with tissue RAS mutation-type;

2. ECOG (Eastern Cooperative Oncology Group) performance score is 0-1;

3. Obtaining informed consent;

4. Surgical specimens or punctured tissue specimens containing tumors can be obtained; 10ml of peripheral blood can be obtained

Exclusion Criteria:

1. The pathology was not confirmed by colonoscopy biopsy or biopsy of metastasis;

2. Colorectal cancer patients with clinical stage I-III;Patients with RAS wild-type metastatic colorectal cancer confirmed by histological genetic testing;Lack of adequate organ functions, such as severe abnormalities in blood, liver and kidney function

Related Conditions & MeSH terms

• Colorectal Cancer Metastatic
• Colorectal Neoplasms

Intervention

Drug:
• Cetuximab
Cetuximab is given In patients with NeoRAS WT

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

References & Publications (4)

Nicolazzo C, Magri V, Marino L, Belardinilli F, Di Nicolantonio F, De Renzi G, Caponnetto S, De Meo M, Giannini G, Santini D, Cortesi E, Gazzaniga P. Genomic landscape and survival analysis of ctDNA "neo-RAS wild-type" patients with originally RAS mutant metastatic colorectal cancer. Front Oncol. 2023 Mar 29;13:1160673. doi: 10.3389/fonc.2023.1160673. eCollection 2023. — View Citation

Osumi H, Takashima A, Ooki A, Yoshinari Y, Wakatsuki T, Hirano H, Nakayama I, Okita N, Sawada R, Ouchi K, Fukuda K, Fukuoka S, Ogura M, Takahari D, Chin K, Shoji H, Kato K, Ishizuka N, Boku N, Yamaguchi K, Shinozaki E. A multi-institutional observational study evaluating the incidence and the clinicopathological characteristics of NeoRAS wild-type metastatic colorectal cancer. Transl Oncol. 2023 Sep;35:101718. doi: 10.1016/j.tranon.2023.101718. Epub 2023 Jun 24. — View Citation

Osumi H, Vecchione L, Keilholz U, Vollbrecht C, Alig AHS, von Einem JC, Stahler A, Striefler JK, Kurreck A, Kind A, Modest DP, Stintzing S, Jelas I. NeoRAS wild-type in metastatic colorectal cancer: Myth or truth?-Case series and review of the literature. Eur J Cancer. 2021 Aug;153:86-95. doi: 10.1016/j.ejca.2021.05.010. Epub 2021 Jun 18. — View Citation

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Detection rate of NeoRAS WT	Proportion of occurrence of neoRAS WT	up to 60 months
Secondary	Objective response rate(ORR) of NeoRAS wild-type patients receiving anti-EGFR therapy	Objective response rate of NeoRAS wild-type patients receiving anti-EGFR (epidermal growth factor receptor) therapy	Follow-up was conducted for 2 years after enrollment
Secondary	Progression-free survival (PFS) in NeoRAS WT patients	Progression-free survival (PFS) : time from enrollment to disease progression from any cause	Follow-up was conducted for 2 years after enrollment
Secondary	Overall survival (OS) in NeoRAS WT patients	Overall survival (OS) : time from enrollment to death from any cause, loss of participants, and time of last follow-up	Follow-up was conducted for 2 years after enrollment