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

Breast Neoplasm Female Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03786575
• Other study ID #: NCC1787
• Status: Recruiting
• Phase: N/A
• Start date: December 1, 2018
• Est. completion date: December 31, 2021

Study information

• Verified date: November 2018
• Source: Peking Union Medical College
• Contact: Fei Ma, Dr.
• Phone: +86-13910217780
• Email: drmafei[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 31, 2021
• Est. primary completion date: February 1, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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:

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

? 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.

Related Conditions & MeSH terms

• Breast Neoplasm Female
• Breast Neoplasms
• Mutation
• Therapeutics

Intervention

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

Locations

Country	Name	City	State
China	National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College

Country where clinical trial is conducted

China, 

Outcome

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