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

Official title

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)

Overview

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.

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.

Interventions

• Drug Fulvestrant
  Fulvestrant 500mg Days 0, 14, 28, then every 28 days
• Drug Capecitabine Oral Product
  Capecitabine 2000mg/m2 twice daily x 14 days followed by 7 days off

Primary outcome measures

• Progression free survival (PFS) [Time frame: Estimated 18 months]

Secondary outcome measures (5)

• Overall Survival (OS) [Time frame: Estimated 60 months]
• Objective Response Rate (ORR) [Time frame: Estimated 18 months]
• Clinical Benefit Rate (CBR) [Time frame: Estimated 18 months]
• Quality Of Life (QOL) [Time frame: Estimated up to 60 months]
• Adverse Events and Serious Adverse Events [Time frame: From informed consent through 28 days following treatment completion]

Eligibility criteria

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);

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 13 centers

• Guangdong Provincial People's Hospital — Guangzhou
• Public Health Institute of Sun Yat-sen University — Guangzhou
• Sun Yat-sen Memorial Hospital, Sun Yat-sen University — Guangzhou
• Sun Yat-sen University Cancer Center — Guangzhou
• The First Affiliated Hospital of Guangzhou University of Chinese Medicine — Guangzhou
• The First Affiliated Hospital of Sun Yat-sen University — Guangzhou
• Shantou Central Hospital — Shantou
• Cancer Hospital, Chinese Academy of Medical Sciences, Shenzhen Center — Shenzhen
• … and 5 more centers

Publications

• Wu W, Yang Y, Chen H, Lu Y, Zeng Y, Zhao J, Du C, Lin Y, Peng P, Huang M, Zhang Y, Ouyang Q, Ding L, Cheng Z, Wen Y, Wu Z, Ye J, Ling L, Wang K, Lu Y, Zou G, Zhong J, Wang H, Lin D, Zeng D, Yao C, Chen Q, Zou L, Wang S, Yu Y, Yuan Z, Wang Y, Yao H. Fulvestrant versus capecitabine as maintenance therapy in hormone receptor-positive, HER2-negative metastatic breast cancer after first-line chemothera PMID 42168151

Identifiers

NCT: NCT04263298 · SYS-C-201801-5010

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗