A Study of the Addition of Metronomic Capecitabine to Standard Adjuvant Therapy in High Risk HER2+ BC paTients

NCT03561740 | Recruiting Phase 3 DMC

• 1 other identifier: SCBCG-006
• Study Type: interventional
• Target: 794
• Locations: 1 country
• Sites: 1

Brief Summary

Breast cancer is the most common malignant tumor in women. Recurrent or metastatic breast cancer is incurable. High risk patients usually have the following characteristics, such as, non-pCR after neoadjuvant therapy, lymph nodes positive, \>2cm tumor size, HER2 overexpression, etc. Intensive targeted or chemo therapy could improve prognosis. Previous studies have shown the efficacy and feasibility of intensive treatment of capecitabine in non-pCR breast cancer patients. Given the metronomic capecitabine therapy is well tolerated, we designed this study to compare the efficacy and safety of adding metronomic capecitabine to standard adjuvant therapy for high risk HER2+ breast cancer patients.

Conditions

Breast Cancer

Keywords

breast cancer; HER2-positive; metronomic chemotherapy; capecitabine; high-risk

Outcome Measures

Primary Outcomes (1)

• Invasive disease-free survival (IDFS)

  Time from randomization to ipsilateral invasive breast tumor recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, or death of any cause

  up to 10 years

Secondary Outcomes (5)

• Invasive disease-free survival including second non-breast cancers

  up to 10 years

• Disease-free survival

  up to 10 years

• Overall survival

  up to 10 years

• Breast cancer specific survival

  up to 10 years

• Distant recurrence-free interval

  up to 10 years

Other Outcomes (1)

• Incidence of adverse events in the treatment of capecitabine

  up to 10 years

Study Arms (2)

Metronomic Capecitabine Group

EXPERIMENTAL

Patients in experimental group (also Metronomic Capecitabine Group) will receive additional metronomic chemotherapy of capecitabine (500mg TID po), begin after the completion of standard adjuvant chemotherapy or surgery if neoadjuvant chemotherapy were administrated, until three weeks after the last cycle of trastuzumab (6mg/kg every 3 weeks).

Drug: capecitabine

Control Group

NO INTERVENTION

Patients in control group will receive standard therapy only, as per the guidelines.

Interventions

capecitabine DRUG

additional metronomic chemotherapy of capecitabine

Also known as: Xeloda

Metronomic Capecitabine Group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Early stage operable HER2-positive primary breast cancer
• Histologically confirmed invasive breast carcinoma
• High risk patients: residual invasive lesions in surgical specimens after neoadjuvant treatment (non-pCR ), Lymph node positive, tumor maximal diameter \>2cm. If patient get neoadjuvant treatment, Systemic therapy must consist of at least 6 cycles of chemotherapy, with a total duration at least 16 weeks, including at least 9 weeks of trastuzumab and at least 9 weeks of taxane-based chemotherapy. Patients may have received an anthracycline as part of preoperative therapy in addition to taxane chemotherapy. Patients receiving dose-dense chemotherapy regimens are eligible, provided at least 8 weeks of taxane-based therapy and at least 8 weeks of trastuzumab have been given.
• Adequate excision: surgical removal of all clinically evident disease in the breast and lymph nodes
• Known hormone receptor status
• Signed written informed consent approved by the study site's Institutional Review Board (IRB)/Ethical Committee (EC)
• Age ≥ 18 years, Age ≤ 70 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Adequate organ function during screening, defined as:
• Absolute neutrophil count ≥ 1200 cells/mm3
• Platelet count ≥ 100000 cells/mm3
• Hemoglobin ≥ 9.0 g/dL; patients may receive red blood cell transfusions to obtain this level
• Serum creatinine 1.5 upper limit of normal (ULN)
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 ULN
• Serum AST and ALT ≤ 1.5 ULN

You may not qualify if:

• Stage IV (metastatic) breast cancer
• History of any prior (ipsi- or contralateral) breast cancer except lobular CIS
• Evidence of clinically evident gross residual or recurrent disease following preoperative therapy and surgery
• An overall response of PD according to the investigator at the conclusion of preoperative systemic therapy
• Treatment with any anti-cancer investigational drug within 28 days prior to commencing study treatment
• History of other malignancy within the last 5 years except for appropriately treated CIS of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other non-breast malignancies with an outcome similar to those mentioned above
• Patients for whom radiotherapy would be recommended for breast cancer treatment but for whom it is contraindicated because of medical reasons (e.g., connective tissue disorder or prior ipsilateral breast radiation)
• Current NCI CTCAE (Version 4.0) Grade ≥ 2 peripheral neuropathy
• History of exposure to the following cumulative doses of anthracyclines:
• Doxorubicin \>240 mg/m2, Epirubicin or Liposomal Doxorubicin-Hydrochloride (Myocet®) \>480 mg/m2 For other anthracyclines, exposure equivalent to doxorubicin \>240 mg/m2
• Cardiopulmonary dysfunction as defined by any of the following:
• History of NCI CTCAE (Version 4.0) Grade ≥ 3 symptomatic CHF or NYHA criteria Class ≥ II Angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease High-risk uncontrolled arrhythmias: i.e., atrial tachycardia with a heart rate \> 100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher-grade AV-block (second degree AV-block Type 2 \[Mobitz 2\] or third degree AV-block) Significant symptoms (Grade ≥ 2) relating to left ventricular dysfunction, cardiac arrhythmia, or cardiac ischemia while or since receiving preoperative therapy.
• History of a decrease in LVEF to \<40% with prior trastuzumab treatment (e.g., during preoperative therapy) Uncontrolled hypertension (systolic blood pressure \>180 mmHg and/or diastolic blood pressure \>100 mmHg) Evidence of transmural infarction on ECG Requirement for continuous oxygen therapy
• Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound-healing disorders; ulcers)
• For female patients, current pregnancy and/or lactation

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Shusen Wang

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Shusen Wang, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shusen Wang, MD

CONTACT

+86-13926168469; wangshs@sysucc.org.cn

Wen Xia, MD

CONTACT

+86-18565557603; xiawen@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 5, 2018
• First Posted: June 19, 2018
• Study Start: July 25, 2018
• Primary Completion: June 15, 2023
• Study Completion (Estimated): December 31, 2028
• Last Updated: July 26, 2018

Record last verified: 2018-07

Locations

CN (1)