Metronomic Capecitabine Plus Aromatase Inhibitor for First Line Treatment in HR(+), Her2(-) Metastatic Breast Cancer

Phase 3

Active, not recruiting

• Conditions: Breast Cancer
• Interventions: Drug: Aromatase Inhibitor; Drug: Capecitabine

• Registration Number: NCT02767661
• Lead Sponsor: Sun Yat-sen University

Brief Summary

The study is designed to compare the clinical benefit following treatment with aromatase inhibitor in combination with metronomic capecitabine versus aromatase inhibitor alone in women with hormone receptor-positive, Her2-negative advanced breast cancer who have not received prior systemic anti-cancer therapies for their advanced/metastatic disease.

Detailed Description

Initial endocrine therapy (ET) is a common choice for hormone receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer (MBC) patients for its good tolerability, low toxicity and durable response. The median time to progression (TTP) of initial ET in HR+, HER2- metastatic patients is about 9 months with aromatase inhibitors (AIs). However, all metastatic patients receiving ET will develop resistance to the conventional endocrine treatments ultimately. So some novel agents, like palbociclib and everolimus, are approved to be effective in improving the efficacy of standard ET. But the fact we have to face is either palbociclib or everolimus is focusing on a single checkpoint of pathway that responsible for resistance of ET. In clinical, there are some patients without an activation of resistance-related pathways have poor response to endocrine therapy. And the mechanisms of resistance to endocrine therapy is complicated and not fully understood. So far, these novel agents have not completely solved the clinical problems of secondary drug-resistance. Maybe a broad spectrum anti-cancer therapy with low toxicity and good tolerability is more practical and promising in the near future. Metronomic chemotherapy is administration of low-dose chemotherapy to induce disease control in metastatic cancer patients, which has low-incidence of adverse effects. More and more evidences showed activity of metronomic therapy in breast cancer. Metronomic therapy with or without endocrine therapy in both metastatic and neoadjuvant setting showed considerable efficacy. Although the concept of combination of chemotherapy and endocrine therapy simultaneously was large abandoned because of previous using tamoxifen and intravenous chemotherapy showing no additional benefit, with better understanding of the biology of endocrine therapy and metronomic chemotherapy, it's worth to evaluate whether endocrine therapy plus low-dose metronomic chemotherapy brings a better clinical benefit rate without sacrificing the quality of patients' life. In this phase III study, we investigate the efficacy and safety of low-dose capecitabine plus AI to treat metastatic HR+, HER2- postmenopausal breast cancer patients.

Study Timeline

• Study First Submitted: 2016-05-07
• Study First Submitted QC: 2016-05-07
• Study First Posted: 2016-05-10
• Study Start: 2017-07-19
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-15
• Last Update Posted: 2024-02-16
• Primary Completion: 2024-05
• Study Completion: 2024-05

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 240

Inclusion Criteria

• Adult women with locoregionally recurrent or metastatic disease not amenable to curative therapy
• Confirmed diagnosis of ER positive/Her2-negative breast cancer
• No prior systemic anti-cancer therapy for locoregionally recurrent or metastatic disease
• Any menopausal status, but premenopausal or perimenopausal patients are required to receive LHRHa treatment
• Measurable disease defined by RECIST version 1.1, or bone-only disease
• Eastern Cooperative Oncology Group (ECOG) 0-2, and life expectancy ≥ 3 months
• Adequate organ and marrow function
• Resolution of all toxic effects of prior therapy or surgical procedures

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Exclusion Criteria

• Patients who have progressed within 2 years of adjuvant endocrine therapy
• Patients who have not received prior endocrine therapy and are eligible to receive fulvestrant as initial therapy
• Patients with advanced, symptomatic, visceral spread that are at risk of life threatening complication in the short term
• Known uncontrolled or symptomatic central nervous system metastases
• Diagnosis of any other malignancy within 3 years prior to randomization (except adequately treated basal or squamous cell skin cancer or cervical carcinoma in situ)
• Serious uncontrolled intercurrent infections or intercurrent medical or psychiatric illness

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Aromatase inhibitor	Aromatase Inhibitor	Aromatase inhibitor (Anastrozole 1 mg, orally once daily or Letrozole 2.5mg, orally once daily or Exemestane 25mg, orally once daily)
Capecitabine+Aromatase inhibitor	Aromatase Inhibitor	Capecitabine, 500mg, orally three times daily in combination with an aromatase inhibitor (Anastrozole 1 mg, orally once daily or Letrozole 2.5mg, orally once daily or Exemestane 25mg, orally once daily)
Capecitabine+Aromatase inhibitor	Capecitabine	Capecitabine, 500mg, orally three times daily in combination with an aromatase inhibitor (Anastrozole 1 mg, orally once daily or Letrozole 2.5mg, orally once daily or Exemestane 25mg, orally once daily)

Primary Outcome Measures

Name	Time	Method
Progress-free survival	Baseline up to approximately 20 months	Time from randomization to the first documentation of objective tumor progression or to death due to any cause without documented progression.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Baseline until death (up to approximately 48 months)	Time from randomization to date of death due to any cause.

Trial Locations

Locations (1)

State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China