The Gene Profiles of Primary and Heterogeneous Metastases of Colorectal Cancer

A Study Comparing the Gene Profiles of Primary and Heterogeneous Metastases of Colorectal Cancer

The incidence and mortality of colorectal cancer in China's cancer disease spectrum is on the rise, and it is a common malignant tumor that harms the health of Chinese residents.In patients with synchronous metastatic colorectal cancer, RAS status is highly consistent in primary focus and metastasis, so NCCN guidelines recommend RAS testing of primary or metastatic tissue is feasible .However, there are also some reports that the difference of RAS status between primary and metastatic lesions was up to 22%.In additiont,there are few studies on whether the gene profile of the metastatic lesion is the same as that of the primary lesion in patients with postoperative heterogeneous metastasis in patients with stage III colorectal cancer.

Study Overview

• Status: Unknown
• Conditions: Metastatic Colorectal Cancer

Detailed Description

The incidence and mortality of colorectal cancer in China's cancer disease spectrum is on the rise, and it is a common malignant tumor that harms the health of Chinese residents. Now NCCN guidelines recommend targeted drugs for the treatment of metastatic colorectal cancer mainly including cetuximab and panizumab whic targeting EGFR , as well as the bevacizumab and arber regofini, etc which targeing anti-angiogenic.Cetuximab and panizumab are only effective in patients with RAS wild type.

Previous studies have shown that In patients with synchronous metastatic colorectal cancer, RAS status is highly consistent in primary focus and metastasis, so NCCN guidelines recommend RAS testing of primary or metastatic tissue is feasible .However, there are also some reports that the difference of RAS status between primary and metastatic lesions was up to 22%.In additiont,there are few studies on whether the gene profile of the metastatic lesion is the same as that of the primary lesion in patients with postoperative heterogeneous metastasis in patients with stage III colorectal cancer.

Therefore, it has important clinical significance to compare the difference of gene profile between metastatic lesion and primary lesion in patients with postoperative metastasis of stage III colorectal cancer.

• Study Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

• Study Contact: Name: Feng Wang, PhD; Phone Number: 86-2087343795; Email: wangfeng@sysucc.org.cn
• Study Contact Backup: Name: Zhida Lv, BS; Phone Number: 86-2087343795; Email: lvzd@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Cancer center of Sun Yat-sen University
      • Contact: Feng Wang, MD, PhD; Phone Number: 86-2087343795; Email: wangfeng@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with postoperative heterochronous metastasis,who has histologically confirmed metastatic colorectal adenocarcinoma and metastases could be punctured by interventional evaluation.In addittion,patients' blood ctDNA and tissues can be used to detect genetic mutations.

Description

Inclusion Criteria:

1. Age ≥ 18 years old and ≤ 75 years old, both men and women;
2. Patients must have histologically confirmed metastatic colorectal adenocarcinoma and metastases can be punctured by interventional evaluation;
3. ECOG: 0 to 2;
4. Expected survival ≥ 12 weeks;
5. Absolute neutrophil count (ANC) ≥ 1.5 × 109 /L; Hemoglobin ≥ 8g / dL; Platelets ≥100×109/L;(According to the normal value of the clinical trial center)
6. Prothrombin time (PT) < 1.5 times the upper normal limit and thrombin time (APTT) < 1.5 times the upper normal limit;
7. Informed consent has been signed.

Exclusion Criteria:

1. Patients had surgery within three weeks will be excluded.
2. Patients have known or suspected brain metastases will be excluded.
3. Pregnant or nursing women will be excluded.
4. Patients with severe uncontrolled systemic disease, such as severe active infection, will be excluded.
5. Patients had other malignancies in the past 5 years will be excluded, except cervical carcinoma in situ or basal cell carcinoma of the skin.
6. Patients who were unable to complete the study or sign valid informed consent for medical, social or psychological reasons, which will be determined by researcher, will be excluded.
7. Organ transplant recipients who need immunosuppressive therapy will be excluded.
8. People have been known to be infected with immunodeficiency virus (HIV) or have been known to be serologically positive for HIV will be excluded.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
primary and metastasis lesion; tissue of colorectal cancer primary lesion and tissue of colorectal cancer metastasis were obtained

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mutation Consistency of metastatic and primary sites of colorectal cancer patients with postoperative metastasis	We do NGS sequencing of both the primary and metastatic tissue sample of the CRC patients. The gene mutation data will be analysis, and the percentage of same and different mutation of the samples will be compared.	through study completion, an average of 2 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mutation Consistency of tissue and blood sample	The gene mutation data will be analysis, and the percentage of same and different mutation of the samples will be reported. The consistency between the gene mutation of ctDNA test in blood and the gene mutation of tissue test is analyzed to determine whether the blood ctDNA test could replace the tissue gene test	through study completion, an average of 2 years.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
prediction accuracy of survival rate	We will use the gene mutation data and follow-up data of the patients to construct a prediction model, and the accuracy of model to anticipating the 2-year survival rate of patients will be analyzed. To analyze the relationship between different gene mutations and patients' recurrence and prognosis, and to clarify the prognostic role of new mutations in heterogeneous metastasis.	through study completion, an average of 2 years.

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Rui-hua Xu, PhD, Sun Yat-sen University

Publications and helpful links

General Publications

• Siyar Ekinci A, Demirci U, Cakmak Oksuzoglu B, Ozturk A, Esbah O, Ozatli T, Celik B, Budakoglu B, Turker I, Bal O, Turan N. KRAS discordance between primary and metastatic tumor in patients with metastatic colorectal carcinoma. J BUON. 2015 Jan-Feb;20(1):128-35.

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2018
• Primary Completion (Anticipated): December 27, 2021
• Study Completion (Anticipated): December 27, 2021

Study Registration Dates

• First Submitted: October 28, 2019
• First Submitted That Met QC Criteria: January 11, 2020
• First Posted (Actual): January 18, 2020

Study Record Updates

• Last Update Posted (Actual): January 22, 2020
• Last Update Submitted That Met QC Criteria: January 17, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: metastasis; mCRC; gene; primary focus; heterogeneous metastasis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: Gene primary versus metastases

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