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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer Metastatic
• Intervention / Treatment: Drug: Cetuximab

• Study Type: Interventional
• Enrollment (Estimated): 1100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Junjie Peng, PhD; Phone Number: +86 13917373312; Email: pengjj@shca.org.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Junjie Peng, PhD; Phone Number: +86 13917373312; Email: pengjj@shca.org.cn

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: RAS mutated metastatic colorectal cancer; 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; Cetuximab is given In patients with NeoRAS WT; Other Names: C225

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection rate of NeoRAS WT	Proportion of occurrence of neoRAS WT	up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Junjie Peng, PhD, Fudan University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2023
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: February 22, 2024
• First Submitted That Met QC Criteria: May 28, 2024
• First Posted (Estimated): June 4, 2024

Study Record Updates

• Last Update Posted (Estimated): June 4, 2024
• Last Update Submitted That Met QC Criteria: May 28, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: ctDNA-neoRASCRC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No