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

NCT ID: NCT02767661

Last Updated: 2024-02-16

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-19
• Study Completion Date: 2024-05-31

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

Capecitabine

Intervention Type: DRUG

Capecitabine, 500mg, orally three times daily (continuously)

Aromatase Inhibitor

Intervention Type: DRUG

Aromatase Inhibitor (Anastrozole, 1mg, orally once daily or Letrozole, 2.5mg, orally once daily or Exemestane , 25mg, orally once daily)

Aromatase inhibitor

Aromatase inhibitor (Anastrozole 1 mg, orally once daily or Letrozole 2.5mg, orally once daily or Exemestane 25mg, orally once daily)

Group Type: ACTIVE_COMPARATOR

Aromatase Inhibitor

Intervention Type: DRUG

Aromatase Inhibitor (Anastrozole, 1mg, orally once daily or Letrozole, 2.5mg, orally once daily or Exemestane , 25mg, orally once daily)

Interventions

Capecitabine

Capecitabine, 500mg, orally three times daily (continuously)

Intervention Type: DRUG

Aromatase Inhibitor

Aromatase Inhibitor (Anastrozole, 1mg, orally once daily or Letrozole, 2.5mg, orally once daily or Exemestane , 25mg, orally once daily)

Intervention Type: DRUG

Other Intervention Names

xeloda; anastrozole; letrozole; exemestane

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

wang shusen

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shusen Wang, MD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

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

Guangzhou, Guangdong, China

Countries

China

References

Hong RX, Xu F, Xia W, Teng YE, Ouyang QC, Zheng QF, Yuan ZY, Chen DS, Jiang KK, Lin Y, Dai Z, Liu XL, Chen QJ, Wu XH, Shi YX, Huang JJ, An X, Xue C, Bi XW, Chen MT, Li H, Yao HR, Zou GR, Huang H, Zhang JM, Wang SS. Metronomic Capecitabine Plus Aromatase Inhibitor as Initial Therapy in Patients With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: The Phase III MECCA Trial. J Clin Oncol. 2025 Apr 10;43(11):1314-1324. doi: 10.1200/JCO.24.00938. Epub 2025 Jan 2.

Reference Type: DERIVED

PMID: 39746176 (View on PubMed)

Other Identifiers

SYSUCC 5010-MECCA

Identifier Type: -

Identifier Source: org_study_id