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Letrozole Plus Metronomic Capecitabine as First-line Treatment for Patients With Recurrent or Metastatic Breast Cancer

Phase 2
Not yet recruiting
Conditions
Metastasis Breast
Registration Number
NCT04942899
Lead Sponsor
Assiut University
Brief Summary

The study is designed to assess the treatment outcomes following treatment with letrozole plus metronomic capecitabine in patients with hormone receptor-positive, Her2-negative advanced breast cancer who have not received prior systemic anti-cancer therapies for their recurrent /metastatic disease.

Detailed Description

Breast cancer is recognized as the commonest cancer in females, and the second commonest malignant tumor, after lung cancer, in overall figures worldwide.

In 2021, an estimated 281,550 new cases of invasive breast cancer are expected to be diagnosed in women in the U.S., along with 49,290 new cases of non-invasive (in situ) breast cancer.

About 43,600 women in the U.S. are expected to die in 2021 from breast cancer. Death rates have been steady in women under 50 since 2007, but have continued to drop in women over 50. The overall death rate from breast cancer decreased by 1% per year from 2013 to 2018. These decreases are thought to be the result of treatment advances and earlier detection through screening.

According to the World Health Organization, breast cancer became the most common cancer globally as of 2021, accounting for 12% of all new annual cancer cases worldwide.

Breast cancer is increasingly recognized as a heterogeneous disease exhibiting substantial differences concerning biological behavior and requiring distinct therapeutic interventions. There has been a continuous decline in mortality over recent years due to improvements in early diagnosis and the increased availability of more effective treatments. However, despite these improvements, The treatment of hormone receptor-positive metastatic breast cancer (MBC) who developed disease progression on first-line hormonal treatment that included aromatase inhibitors (AI) represents a challenge as those patients ultimately develop resistant disease unresponsive to standard lines of estrogen receptors (ER) blockade. Capecitabine is an oral chemotherapy that mimics continuous infusion of 5-FU with known activity in MBC. It might be preferred because of its tolerability and relatively lower toxicity than other chemotherapeutic agents. Metronomic chemotherapy is defined as the frequent (daily, many times a week, or weekly) or continuous administration of low dose chemotherapeutic agents, without prolonged drug-free intervals. This way of administration improves the antiangiogenic activity of chemotherapy. Another important advantage of this approach is the significant reduction in toxicity. Capecitabine's pharmacokinetics and high safety profile make it a suitable drug for metronomic administration. Many studies reported that the overall response rate can be improved by (15.8-21.7%) when metronomic chemotherapy is combined with aromatase inhibitors. This combination can also decrease the level of both the Ki-67 index and VEGF-A significantly in the tumor tissue. It was reported that the patients who received letrozole plus metronomic chemotherapy achieved a higher overall response rate (ORR) than those who received letrozole alone (87.7% vs 71.9% respectively.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
Female
Target Recruitment
70
Inclusion Criteria
  • Female patients > 18 years old with loco regionally recurrent or metastatic disease not amenable to curative therapy
  • Confirmed diagnosis of hormonal receptor positive (HR+)/Her2-negative breast cancer
  • If the patient is pre-/peri- menopausal, a luteinizing hormone releasing hormone (LHRH) agonist will be given for at least 28 days before randomization or ovarian ablation or suppression by surgery or radiotherapy
  • Measurable disease defined by RECIST version 1.1,
  • Eastern Cooperative Oncology Group (ECOG) 0-2
  • Adequate organ and marrow function
Exclusion Criteria
  • Patients with advanced, symptomatic visceral spread (visceral crisis)
  • Patients diagnosed with central nervous system metastases
  • Second primary malignancy

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
tumor response1 year

tumor response in form of change tumor size

Secondary Outcome Measures
NameTimeMethod
progression free survival1 year

decrease sites of metastasis

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