Fulvestrant Versus Capecitabine as Maintenance Therapy After First-line Chemotherapy in Patients With HR+/HER2- Metastatic Breast Cancer

A Randomized, Multi-center, Open-label, Phase III Trial of Fulvestrant Versus Capecitabine as Maintenance Therapy After First-line Chemotherapy in Patients With Hormone Receptor Positive, Human Epidermal Growth Factor Receptor-2 Negative Metastatic Breast Cancer (FAMILY)

This phase III trial aims to compare the efficacy and safety of fulvestrant or capecitabine as maintenance therapy after first-line chemotherapy in hormone receptor-positive, human epidermal growth factor receptor-2 negative metastatic breast cancer.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Fulvestrant; Drug: Capecitabine Oral Product

Detailed Description

Metastatic breast cancer (MBC) is incurable. Although first-line endocrine therapy is preferred to hormone receptor positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) MBC, chemotherapy may be reserved as the initial treatment for patients with rapid clinical progression, life-threatening visceral metastases, and need for rapidly symptom control. Either prolonged chemotherapy or endocrine therapy may be used as maintenance after disease control. However, which maintenance strategy is superior in terms of delaying disease progression as well as maintaining quality of life (QOL) remains uncertain. This phase III trial aims to compare the efficacy and safety of fulvestrant or capecitabine as maintenance therapy after first-line chemotherapy in HR+/HER2- MBC.

• Study Type: Interventional
• Enrollment (Anticipated): 210
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Herui Yao, PhD; Phone Number: +86 13500018020; Email: yaoherui@mail.sysu.edu.cn
• Study Contact Backup: Name: Wenjing Wu, PhD; Phone Number: +86 15902045077; Email: wuwenjing@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Sun yat-sen University Cancer Center
      • Contact: Shusen Wang, PhD
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • The First Affiliated Hospital of Sun Yat-sen University
      • Contact: Ying Lin, PhD
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Guangdong Provincial People's Hospital
      • Contact: Kun Wang, PhD
      • Principal Investigator: Kun Wang, PhD
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
      • Contact: Herui Yao, PhD; Phone Number: +86 13500018020; Email: yaoherui@mail.sysu.edu.cn
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Public Health Institute of Sun Yat-sen University
      • Contact: Li Ling, PhD
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • The First Affiliated Hospital of Guangzhou University of Chinese Medicine
      • Contact: Mei Huang, MD
    • Shantou, Guangdong, China
      • Recruiting
      • Shantou Central Hospital
      • Contact: Zhiyong Wu, MD
    • Shenzhen, Guangdong, China
      • Recruiting
      • Cancer Hospital, Chinese Academy of Medical Sciences, Shenzhen Center
      • Contact: Caiwen Du, PhD
    • Shenzhen, Guangdong, China
      • Not yet recruiting
      • ShenZhen People's Hospital
      • Contact: Ruilian Xu, Master
    • Zhangjiang, Guangdong, China
      • Recruiting
      • Affiliated Hospital of Guangdong Medical University
      • Contact: Ying Zhang, MD
    • Zhuhai, Guangdong, China
      • Recruiting
      • Fifth Subsidiary Sun Yat-sen University Hospital
      • Contact: Peijian Peng, PhD
  • Guangxi
    • Nanning, Guangxi, China
      • Recruiting
      • Affiliated Cancer Hospital of Guangxi Medical University
      • Contact: Yongkui Lu, MD
  • Hunan
    • Changsha, Hunan, China
      • Recruiting
      • Hunan Cancer Hospital
      • Contact: Quchang Ouyang, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Adult female patients with advanced breast cancer diagnosed by pathology (aged 18-75, including 18 and 75 years old), not suitable for surgical resection or radiation therapy for the purpose of cure;
• Pathological examination confirmed ER and / or PR positive, HER-2 negative (Positive ER expression: immunohistochemistry >1% tumor cell staining; Positive PR expression: immunohistochemistry >1% tumor cell staining; HER-2 negative: immunohistochemistry is 0,1+, or FISH/CISH negative when immunohistochemistry is 2+);
• Patients with advanced breast cancer who have no disease progression after a 4-8-course first-line chemotherapy regimen (the effect is evaluated as complete response/ partial response/ stable disease). Capecitabine monotherapy as first-line chemotherapy is allowed and the courses of treatment should be limited to 6.
• WHO physical status 0-1 points, estimated lifetime at least 3 months;
• Imaging examinations within 3 weeks before enrollment were required for assessing tumor lesions before maintenance treatment (Examination results from local Tertiary A hospital are available);
• Previous treatment-related toxicity should be relieved to ≤ Grade 1 according to NCI CTCAE (version 4.03) before randomization (Except for hair loss and other toxicities that are not at risk to the patient's safety based on the investigator's judgment);
• The routine blood test was normal within 1 week before enrollment: WBC ≥3.0×10^9／L, b. ANC ≥1.5×10^9／L, c. PLT ≥100×10^9／L;
• The liver and kidney function test was normal within 1 week before enrollment (Take the normal value of the laboratory of each research center as the standard): a. TBIL≤1.5× Upper Limit of Normal (ULN)b. ALT/AST≤2.5×ULN（Liver metastasis patients ≤5xULN） c. Serum Cr ≤1.5×ULN, or Ccr ≥60 ml/min;
• Informed consent form signed before enrollment.

Exclusion Criteria:

Cannot be grouped if any of the following is true:

• Newly developed central nervous system metastasis or symptom control of central nervous system is less than 4 weeks. (Patients with asymptomatic brian metastases which was stable more than 4 weeks by imaging assessment and do not need corticosteroid therapy are allowed to enrollment)
• Diagnosis of any other malignant tumor within 3 years before randomization, except for adequately treated basal cells or squamous cell skin cancer or cervical cancer in situ;
• Endocrine therapy for advanced disease;
• Pregnant or breast-feeding patients;
• Patients with accompanying disease or situation that may interfere with the study, or any serious medical problems that may affect the safety of the subject (for example, uncontrolled heart disease or high blood pressure, active or uncontrolled infection, active hepatitis B virus infection);
• Patients who were unable to tolerate capecitabine toxicity were first identified in first-line treatment;
• Patients with recurrent metastatic disease within 2 years of adjuvant endocrine therapy (including 2 years);

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Fulvestrant Group; Fulvestrant 500mg Days 0, 14, 28, then every 28 days	Drug: Fulvestrant; Fulvestrant 500mg Days 0, 14, 28, then every 28 days; Other Names: Experimental group
ACTIVE_COMPARATOR: Capecitabine Group; Capecitabine 2000mg/m2 twice daily x 14 days followed by 7 days off	Drug: Capecitabine Oral Product; Capecitabine 2000mg/m2 twice daily x 14 days followed by 7 days off; Other Names: Active Comparator control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	From enrollment to progression or death (for any reason)	Estimated 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events and Serious Adverse Events	Safety	From informed consent through 28 days following treatment completion
Overall Survival (OS)	From enrollment to death (for any reason)	Estimated 60 months
Objective Response Rate (ORR)	Ratio of CR and PR in all subjects	Estimated 18 months
Clinical Benefit Rate (CBR)	Ratio of CR,PR and SD greater than or equal to 24 weeks in all subjects	Estimated 18 months
Quality Of Life (QOL)	All patients need to fill in the Functional Assessment of Cancer Therapy-Breast (FACT-B), a 44-item self-report instrument designed to measure multidimensional quality of life (QL) in patients with breast cancer.	Estimated up to 60 months

Collaborators and Investigators

• Sponsor: Herui Yao
• Investigators: Principal Investigator: Shusen Wang, PhD, Sun Yat-sen University; Principal Investigator: Kun Wang, PhD, Guangdong Provincial People's Hospital; Principal Investigator: Peijian Peng, PhD, Fifth Subsidiary Sun Yat-sen University Hospital; Principal Investigator: Li Ling, PhD, Public Health Institute of Sun Yat-sen University; Principal Investigator: Yongkui Lu, MD, Affiliated Cancer Hospital of Guangxi Medical University; Principal Investigator: Quchang Ouyang, PhD, Hunan Cancer Hospital; Principal Investigator: Ying Lin, phD, First Affiliated Hospital, Sun Yat-Sen University; Principal Investigator: Ying Zhang, MD, The Affiliated Hospital of Guangdong Medical College; Principal Investigator: Mei Huang, MD, The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine; Principal Investigator: Zhiyong Wu, MD, Shantou Central Hospitalv; Principal Investigator: Cai'wen Du, PhD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2018
• Primary Completion (ANTICIPATED): May 1, 2025
• Study Completion (ANTICIPATED): May 1, 2030

Study Registration Dates

• First Submitted: February 4, 2020
• First Submitted That Met QC Criteria: February 7, 2020
• First Posted (ACTUAL): February 10, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 30, 2022
• Last Update Submitted That Met QC Criteria: September 28, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Capecitabine; Fulvestrant
• Other Study ID Numbers: SYS-C-201801-5010

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