Metronomic Capecitabine Plus Aromatase Inhibitor for First Line Treatment in HR(+), Her2(-) Metastatic Breast Cancer (MECCA)
Primary Purpose
Breast Cancer
Status
Active
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Capecitabine
Aromatase Inhibitor
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring metronomic capecitabine, aromatase inhibitor, first line treatment, metastatic breast cancer
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 advanced ER+ disease
- Any menopausal status
- On a luteinizing hormone releasing hormone (LHRH) agonist for at least 28 days, if pre-/peri-menopausal, and willing to switch to goserelin (Zoladex ®) at time of randomization
- Measurable disease defined by RECIST version 1.1, or bone-only disease
- Eastern Cooperative Oncology Group (ECOG) 0-1
- Adequate organ and marrow function
- Resolution of all toxic effects of prior therapy or surgical procedures
- Patient must agree to provide tumor tissue from metastatic tissue at baseline
Exclusion Criteria:
- 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
- Second primary malignancy(except in situ carcinoma of the cervix or adequately treated nonmelanomatous carcinoma of the skin)
- Serious uncontrolled intercurrent infections or intercurrent medical or psychiatric illness
Sites / Locations
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Capecitabine+Aromatase inhibitor
Aromatase inhibitor
Arm Description
Capecitabine, 625mg/m2, orally twice 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)
Aromatase inhibitor (Anastrozole 1 mg, orally once daily or Letrozole 2.5mg, orally once daily or Exemestane 25mg, orally once daily)
Outcomes
Primary Outcome Measures
Progress-free survival
Time from randomization to the first documentation of objective tumor progression or to death due to any cause.
Secondary Outcome Measures
Overall Survival
Time from randomization to date of death due to any cause.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02767661
Brief Title
Metronomic Capecitabine Plus Aromatase Inhibitor for First Line Treatment in HR(+), Her2(-) Metastatic Breast Cancer
Acronym
MECCA
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 19, 2017 (Actual)
Primary Completion Date
May 2024 (Anticipated)
Study Completion Date
May 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
metronomic capecitabine, aromatase inhibitor, first line treatment, metastatic breast cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
240 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Capecitabine+Aromatase inhibitor
Arm Type
Experimental
Arm Description
Capecitabine, 625mg/m2, orally twice 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)
Arm Title
Aromatase inhibitor
Arm Type
Active Comparator
Arm Description
Aromatase inhibitor (Anastrozole 1 mg, orally once daily or Letrozole 2.5mg, orally once daily or Exemestane 25mg, orally once daily)
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
xeloda
Intervention Description
Capecitabine, 625mg/m2, orally twice daily (continuously)
Intervention Type
Drug
Intervention Name(s)
Aromatase Inhibitor
Other Intervention Name(s)
anastrozole, letrozole, exemestane
Intervention Description
Aromatase Inhibitor (Anastrozole, 1mg, orally once daily or Letrozole, 2.5mg, orally once daily or Exemestane , 25mg, orally once daily)
Primary Outcome Measure Information:
Title
Progress-free survival
Description
Time from randomization to the first documentation of objective tumor progression or to death due to any cause.
Time Frame
Baseline up to approximately 20 months
Secondary Outcome Measure Information:
Title
Overall Survival
Description
Time from randomization to date of death due to any cause.
Time Frame
Baseline until death (up to approximately 48 months)
Other Pre-specified Outcome Measures:
Title
Objective Response Rate (ORR)
Description
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.
Time Frame
Baseline up to approximately 20 months
Title
Disease Control Rate (DCR)
Description
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.
Time Frame
Baseline up to approximately 20 months
Title
Change From Baseline in Euro Quality of Life (EQ-5D)- Health State Profile Utility
Description
Instrument designed to assess health status in terms of a single index value or utility score.
Time Frame
Baseline up to approximately 20 months
Title
Change From Baseline in Functional Assessment od Cancer therapy -Breast (FACT-B)
Description
Instrument designed to assess patient concerns relating to breast cancer
Time Frame
Baseline up to approximately 20 months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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 advanced ER+ disease
Any menopausal status
On a luteinizing hormone releasing hormone (LHRH) agonist for at least 28 days, if pre-/peri-menopausal, and willing to switch to goserelin (Zoladex ®) at time of randomization
Measurable disease defined by RECIST version 1.1, or bone-only disease
Eastern Cooperative Oncology Group (ECOG) 0-1
Adequate organ and marrow function
Resolution of all toxic effects of prior therapy or surgical procedures
Patient must agree to provide tumor tissue from metastatic tissue at baseline
Exclusion Criteria:
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
Second primary malignancy(except in situ carcinoma of the cervix or adequately treated nonmelanomatous carcinoma of the skin)
Serious uncontrolled intercurrent infections or intercurrent medical or psychiatric illness
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shusen Wang, MD
Organizational Affiliation
Sun Yat-sen University
Official's Role
Principal Investigator
Facility Information:
Facility Name
State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Metronomic Capecitabine Plus Aromatase Inhibitor for First Line Treatment in HR(+), Her2(-) Metastatic Breast Cancer
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