Clinical trial NCT02767661: Metronomic Capecitabine Plus Aromatase Inhibitor for First Line Treatment in HR(+), Her2(-) Metastatic Breast Cancer
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Keywords: metronomic capecitabine
aromatase inhibitor
first line treatment
metastatic breast cancer
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2016-05-10
Enrollment: 240
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progress-free survival
timeFrame: Baseline up to approximately 20 months
Secondary outcomes:
measure: Overall Survival
timeFrame: Baseline until death (up to approximately 48 months)
Other outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Baseline up to approximately 20 months
measure: Disease Control Rate (DCR)
timeFrame: Baseline up to approximately 20 months
measure: Adverse events
timeFrame: Baseline up to approximately 20 months
measure: Quality-of-life score
timeFrame: Baseline up to approximately 20 months
measure: Quality-of-life score
timeFrame: Baseline up to approximately 20 months
Locations:
city: Guangzhou
country: China
facility: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Shusen Wang, MD
role: PRINCIPAL_INVESTIGATOR
References: