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

NCT06440902 | Recruiting Phase 2

• 1 other identifier: ctDNA-neoRASCRC
• Study Type: interventional
• Target: 1,100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Colorectal Cancer Metastatic

Outcome Measures

Primary Outcomes (1)

• Detection rate of NeoRAS WT

  Proportion of occurrence of neoRAS WT

  up to 60 months

Secondary Outcomes (3)

• Objective response rate(ORR) of NeoRAS wild-type patients receiving anti-EGFR therapy

  Follow-up was conducted for 2 years after enrollment

• Progression-free survival (PFS) in NeoRAS WT patients

  Follow-up was conducted for 2 years after enrollment

• Overall survival (OS) in NeoRAS WT patients

  Follow-up was conducted for 2 years after enrollment

Study Arms (1)

RAS mutated metastatic colorectal cancer

EXPERIMENTAL

RAS mutated metastatic colorectal cancer were routinely treated after enrollment. When the disease progression was confirmed by imaging, peripheral blood ctDNA detection was performed to observe whether they were transformed into NeoRAS wild-type patients. If NeoRAS wild- type was detected, the anti-EGFR therapy may be considered as the following therapy for patients.

Drug: Cetuximab

Interventions

Cetuximab DRUG

Cetuximab is given In patients with NeoRAS WT

Also known as: C225

RAS mutated metastatic colorectal cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Metastatic colorectal cancer with tissue RAS mutation-type;
• ECOG (Eastern Cooperative Oncology Group) performance score is 0-1;
• Obtaining informed consent;
• Surgical specimens or punctured tissue specimens containing tumors can be obtained; 10ml of peripheral blood can be obtained

You may not qualify if:

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

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Related Publications (4)

• 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.

  PMID: 33538338 BACKGROUND

• 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.

  PMID: 37364334 BACKGROUND

• 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.

  PMID: 37064137 BACKGROUND

• 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.

  PMID: 34153718 BACKGROUND

MeSH Terms

Interventions

Cetuximab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Junjie Peng, PhD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Junjie Peng, PhD

CONTACT

+86 13917373312; pengjj@shca.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 22, 2024
• First Posted: June 4, 2024
• Study Start: December 28, 2023
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: June 4, 2024

Record last verified: 2024-05

Locations

CN (1)