Clinical Value of Next Generation Sequencing in Endocrine Therapy for Advanced Hormone Receptor Positive/HER-2 Negative Breast Cancer

To determine the landscape of gene mutation before and after endocrine therapy, to search for molecular markers of endocrine therapy efficacy, and to explore the clinical value of using NGS detection of ctDNA to guide precise endocrine therapy in patients with advanced breast cancer. The primary endpoints were progression-free survival (PFS), and the secondary endpoints included overall survival time (OS), adverse events (AE), and severe adverse events (SAE).

Study Overview

• Status: Unknown
• Conditions: Breast Neoplasm Female; Mutation; Therapeutics
• Intervention / Treatment: Diagnostic test: Next Generation Sequencing (NGS) detection

Detailed Description

Before treatment, the patients in the study group underwent NGS detection of ctDNA and formulated treatment plan according to the test results: 1) those with ESR1 mutation and who did not use fulvestrant before, preferred fulvestrant; 2) those with abnormal activation of PI3K/Akt/mTOR pathway signal, preferred mTOR inhibitor combined with endocrine therapy; 3) those with HER-2 sensitive point mutation, preferred anti-HER-2 therapy combined with endocrine therapy; 4) PDGFR mutation, preferential use of PDGFR inhibitors combined with endocrine therapy; 5) no significant gene mutation, making endocrine therapy plan according to the actual clinical situation. After 2 months of endocrine therapy, all patients underwent NGS detection of ctDNA, and the efficacy was evaluated according to RECIST v1.1 standard. If the efficacy evaluation is effective, continue the current treatment and re-evaluate the efficacy every two months; if the efficacy evaluation is ineffective (progress), then withdraw from this study. The vital signs, blood routine, liver and kidney functions and imaging examinations were examined at least every two months in the patients in the study group, and the curative effect was evaluated according to RECIST v1.1 standard.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fei Ma, Dr.; Phone Number: +86-13910217780; Email: drmafei@126.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
    • Contact: Fei Ma, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Age ≥18 years, female；
2. Pathologically and immunohistochemically confirmed ER-positive/HER-2-negative patients with advanced breast cancer；
3. According to RECIST standard, lesions can be measured (primary lesion length > 1.0 cm or lymph node diameter > 1.5 cm)；
4. Previous endocrine therapy resistance, preparation for second-or-above-line endocrine therapy；
5. No visceral crisis；
6. ECOG PS score: 0-2 points;

7. Laboratory criteria:

   ① white blood cells were more than 4 x 109 /L, and neutrophil count (ANC) was more than 1.5 x 109 /L.

   ② platelet (>100 *109/L); hemoglobin (>10g/dL); serum creatinine (<1.5 *normal value) upper limit (ULN); aspartate aminotransferase (AST) (<2.5 *ULN); alanine aminotransferase (ALT) (<2.5 *ULN); total bilirubin (<1.5 *ULN); serum creatinine (<1.5 *ULN);

8. the volunteers voluntarily joined the study, signed informed consent, and had good compliance and follow-up.

Exclusion Criteria:

1. Pregnant or lactation woman
2. With mental disease
3. With severe infection or active gastrointestinal ulcers
4. With severe liver disease (such as cirrhosis), kidney disease, respiratory disease or diabetes
5. taking part or participating in other clinical trials within one month.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: NGS detection group; Before treatment, the patients in the study group underwent NGS detection of ctDNA and formulated endocrine treatment plan according to the test results. After 2 months of endocrine therapy, all patients underwent NGS detection of ctDNA, and the efficacy was evaluated according to RECIST v1.1 standard.	Diagnostic test: Next Generation Sequencing (NGS) detection; The NGS detection panel is designed by our team and covers genes that are clinically useful and have definite guiding significance for endocrine therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	From date of first use endocrine treatment until the date of first documented progression or date of death from any cause, whichever came first	up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs)	Adverse events (AEs) and laboratory tests graded according to the NCI CTCAE (version 4.0)	up to 36 months
Overall survival (OS)	Time from first use endocrine treatment to death	up to 60 months

Collaborators and Investigators

• Sponsor: Peking Union Medical College

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Anticipated): February 1, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: December 21, 2018
• First Submitted That Met QC Criteria: December 21, 2018
• First Posted (Actual): December 26, 2018

Study Record Updates

• Last Update Posted (Actual): June 20, 2019
• Last Update Submitted That Met QC Criteria: June 19, 2019
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Breast Neoplasm; Next Generation Sequencing; Endocrine Therapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: NCC1787

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes