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

A Phase 3 Randomized Controlled Study of Metronomic Capecitabine Combined With Aromatase Inhibitor Versus Aromatase Inhibitor Alone for First Line Treatment in Hormone Receptor-positive, Her2-negative Metastatic Breast Cancer

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Aromatase Inhibitor; Drug: Capecitabine

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 Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aromatase inhibitor; Aromatase inhibitor (Anastrozole 1 mg, orally once daily or Letrozole 2.5mg, orally once daily or Exemestane 25mg, orally once daily)	Drug: Aromatase Inhibitor; Aromatase Inhibitor (Anastrozole, 1mg, orally once daily or Letrozole, 2.5mg, orally once daily or Exemestane , 25mg, orally once daily); Other Names: exemestane; letrozole; anastrozole
Experimental: Capecitabine+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)	Drug: Aromatase Inhibitor; Aromatase Inhibitor (Anastrozole, 1mg, orally once daily or Letrozole, 2.5mg, orally once daily or Exemestane , 25mg, orally once daily); Other Names: exemestane; letrozole; anastrozole; Drug: Capecitabine; Capecitabine, 500mg, orally three times daily (continuously); Other Names: xeloda

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Time from randomization to date of death due to any cause.	Baseline until death (up to approximately 48 months)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective response is defined as a complete response (CR) or partial response (PR) according to RECIST v.1.1. recorded from randomization until disease progression or death due to any cause.	Baseline up to approximately 20 months
Disease Control Rate (DCR)	Disease control is defined as complete response (CR), partial response (PR), or stable disease (SD) >24 weeks according to the RECIST version 1.1 recorded in the time period between randomization and disease progression or death to any cause.	Baseline up to approximately 20 months
Adverse events	Adverse events, serious adverse events, and laboratory tests will be analyzed and summarized according to severity.	Baseline up to approximately 20 months
Quality-of-life score	The Functional Assessment of Cancer Therapy - Breast (FACT-B) version 4 questionnaire will be distributed to the patients by the study site personnel and will be filled out by the patients independently. Final scores (FACT-B-Total) of all subscales range from 0 to 148, where 148 represents the most favorable score and accordingly a highest QoL.	Baseline up to approximately 20 months
Quality-of-life score	EORTC QLQ-BR23 questionnaire will be distributed to the patients by the study site personnel and will be filled out by the patients independently.	Baseline up to approximately 20 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Shusen Wang, MD, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2017
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: May 7, 2016
• First Submitted That Met QC Criteria: May 7, 2016
• First Posted (Estimated): May 10, 2016

Study Record Updates

• Last Update Posted (Actual): February 16, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: aromatase inhibitor; metastatic breast cancer; metronomic capecitabine; first line treatment
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Steroid Synthesis Inhibitors; Estrogen Antagonists; Capecitabine; Letrozole; Anastrozole; Exemestane; Aromatase Inhibitors
• Other Study ID Numbers: SYSUCC 5010-MECCA

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