Back to resultsStudy of Apatinib Combined With Oral Vinorelbine in Metastatic HER2 Negative Breast Cancer
Primary Purpose
Breast Cancer
Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Apatinib
Oral Vinorelbine
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- Age between 18 and 75 year-old women; HER2 negative(immunohistochemistry or fluorescence in situ hybridization);
- ECOG score: 0-1, expected survival time ≥ 3months;
- Pathologically or cytologically confirmed breast cancer;
- Anthracycline- / taxane- pretreated (adjuvant, neoadjuvant) breast cancer patients who have failed from 1-2 standard chemotherapies after recurrence and metastasis;
- According to RECIST 1.1, exist at least ≥1 measurable lesion(CT >1cm，other examination >2cm) ;
The patients have enough organ function. The laboratory test indexes must comply with the following requirements:
Blood routine: neutrophil≥1.5G/L, platelet count ≥80G/L, hemoglobin ≥90g/L Liver function: serum bilirubin ≤ 1.5 times the upper limit of normal value; ALT and AST≤2.5 times the upper limit of normal value; ALT and AST≤5 times the upper limit of normal value when liver metastasis Renal function: serum creatinine ≤ 1.0times the upper limit of normal value, creatinine clearance >50ml/min（Cockcroft-Gault formula)
- Women of child-bearing age should be carried out pregnancy test (serum or urine) within 7 days before recruit, the results should be negative; and are willing to adopt the appropriate methods of contraception during the trial and 8 weeks after last administration；
- Can swallow oral drugs;
- The patients have good compliance to the therapy and follow-up to be scheduled and are able to understand the study protocol and sign the Informed Consent Form.
Exclusion Criteria:
- The patients in pregnancy or lactation growth period and did not take effective contraception;
- The patients who received ≥3 chemotherapies（Do not include endocrine therapy）after recurrence and metastasis; involved in other clinical trials four weeks prior to the start of the study;
- The patients with a variety of factors that affect the oral administration and absorption of drugs；
- The patients previously received anti-VEFG of anti-VEGFR therapies；
- The patients with rapid progression of viscera invasion(liver lesion >1/2 viscera area or liver dysfunction);
- The patients have uncontrollable mental illness.
- The patients who had serious adverse effect to oral vinorelbine or were allergic to vinorelbine.
- The patients who have only bone metastasis without other measurable lesion;
- The patients experience severe cardiovascular diseases;
- The patients experience severe upper gastrointestinal ulcer or malabsorption syndrome.
- Abnormal bone marrow functions(neutrophil<1.5G/L, platelet count <75G/L, hemoglobin <90g/L)；
- Abnormal renal function(serum creatinine > 1.5 times the upper limit of normal value)；
- Abnormal liver function(serum bilirubin ≤ 1.5 times the upper limit of normal value);
- The patients have uncontrollable brain metastasis;
- The patients do not have good compliance to the therapy.
Sites / Locations
- Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
lapatinib+oral vinorelbine
Arm Description
apatinib 425/500mg qd, 21days/cycle oral vinorelbine 60mg/m2 d1, 8, 15 21days/cycle*3cycles, after 3 cycles: 80mg/m2 d1, 8, 15 21days/cycle
Outcomes
Primary Outcome Measures
Progression free survival (PFS) among metastatic HER2 negative breast cancer treated with apatinib and oral vinorelbine
Secondary Outcome Measures
remission rate (RR) among metastatic HER2 negative breast cancer treated with apatinib and oral vinorelbine
overall survival (OS) among metastatic HER2 negative breast cancer treated with apatinib and oral vinorelbine
overall response rate (ORR) among metastatic HER2 negative breast cancer treated with apatinib and oral vinorelbine
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Potential biomarkers to predict efficacy, drug resistance and side effects of anti-angiogenic therapy plus chemotherapy in advanced breast cancer.
Full Information
NCT ID
NCT02768415
First Posted
May 4, 2016
Last Updated
June 18, 2019
Sponsor
Chinese Academy of Medical Sciences
1. Study Identification
Unique Protocol Identification Number
NCT02768415
Brief Title
Study of Apatinib Combined With Oral Vinorelbine in Metastatic HER2 Negative Breast Cancer
Official Title
Phase II Study of Apatinib Combined With Oral Vinorelbine in Pretreated Metastatic HER2 Negative Breast Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
June 2019
Overall Recruitment Status
Unknown status
Study Start Date
June 2016 (Actual)
Primary Completion Date
January 2018 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese Academy of Medical Sciences
4. Oversight
5. Study Description
Brief Summary
The hypothesis of this study is to discover if the all-oral therapy with apatinib plus oral vinorelbine can shrink or slow the growth of pretreated HER2 negative metastatic breast cancer.
Detailed Description
Apatinib is an orally administered second-generation blocker of the phosphorylation of the tyrosine residues within the intracellular domain of VEGF receptor 2 (VEGFR2). A prospective, open label, phase II multicenter trial of apatinib in heavily pretreated patients with metastatic triple-negative breast cancer demonstrated that the daily dose of apatinib 500 mg/day is active in pretreated metastatic TNBC with encouraging rates of disease stabilization and PFS.
Vinorelbine is a highly active drug in the treatment of MBC, both as a single agent or in combination regimens, and is well tolerated, with a low incidence of severe toxicity. Clinical trials demonstrated oral NVB provided comparable effectiveness to iv NVB. and oral availability allows using different schedules.
The NCCN guideline introduces that combination chemotherapy is one of the standard treatment options in metastatic breast cancer, especially in patients with visceral metastases and/or need of rapid symptom or disease control.
Theoretically, anti-angiogenesis regimen combined with chemotherapy may present increasing therapeutic effect. Related researches are urgently needed to find optimal combined therapy.
The hypothesis of this study is to discover if the all-oral therapy with apatinib plus oral vinorelbine can shrink or slow the growth of pretreated HER2 negative breast cancer. The safety of the combination will also be studied. Patients physical state, symptoms, changes in the size of the tumor, and laboratory findings obtained while on-study will help the research team decide if this combination is safe and effective in pretreated HER2 negative metastatic breast cancer patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
lapatinib+oral vinorelbine
Arm Type
Experimental
Arm Description
apatinib 425/500mg qd, 21days/cycle
oral vinorelbine 60mg/m2 d1, 8, 15 21days/cycle*3cycles, after 3 cycles: 80mg/m2 d1, 8, 15 21days/cycle
Intervention Type
Drug
Intervention Name(s)
Apatinib
Intervention Type
Drug
Intervention Name(s)
Oral Vinorelbine
Primary Outcome Measure Information:
Title
Progression free survival (PFS) among metastatic HER2 negative breast cancer treated with apatinib and oral vinorelbine
Time Frame
up to 1 year after the last patient enrolled
Secondary Outcome Measure Information:
Title
remission rate (RR) among metastatic HER2 negative breast cancer treated with apatinib and oral vinorelbine
Time Frame
up to 1 year after the last patient enrolled
Title
overall survival (OS) among metastatic HER2 negative breast cancer treated with apatinib and oral vinorelbine
Time Frame
up to 1 year after the last patient enrolled
Title
overall response rate (ORR) among metastatic HER2 negative breast cancer treated with apatinib and oral vinorelbine
Time Frame
up to 1 year after the last patient enrolled
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame
up to 1 year after the last patient enrolled
Title
Potential biomarkers to predict efficacy, drug resistance and side effects of anti-angiogenic therapy plus chemotherapy in advanced breast cancer.
Time Frame
up to 1 year after the last patient enrolled
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age between 18 and 75 year-old women; HER2 negative(immunohistochemistry or fluorescence in situ hybridization);
ECOG score: 0-1, expected survival time ≥ 3months;
Pathologically or cytologically confirmed breast cancer;
Anthracycline- / taxane- pretreated (adjuvant, neoadjuvant) breast cancer patients who have failed from 1-2 standard chemotherapies after recurrence and metastasis;
According to RECIST 1.1, exist at least ≥1 measurable lesion(CT >1cm，other examination >2cm) ;
The patients have enough organ function. The laboratory test indexes must comply with the following requirements:
Blood routine: neutrophil≥1.5G/L, platelet count ≥80G/L, hemoglobin ≥90g/L Liver function: serum bilirubin ≤ 1.5 times the upper limit of normal value; ALT and AST≤2.5 times the upper limit of normal value; ALT and AST≤5 times the upper limit of normal value when liver metastasis Renal function: serum creatinine ≤ 1.0times the upper limit of normal value, creatinine clearance >50ml/min（Cockcroft-Gault formula)
Women of child-bearing age should be carried out pregnancy test (serum or urine) within 7 days before recruit, the results should be negative; and are willing to adopt the appropriate methods of contraception during the trial and 8 weeks after last administration；
Can swallow oral drugs;
The patients have good compliance to the therapy and follow-up to be scheduled and are able to understand the study protocol and sign the Informed Consent Form.
Exclusion Criteria:
The patients in pregnancy or lactation growth period and did not take effective contraception;
The patients who received ≥3 chemotherapies（Do not include endocrine therapy）after recurrence and metastasis; involved in other clinical trials four weeks prior to the start of the study;
The patients with a variety of factors that affect the oral administration and absorption of drugs；
The patients previously received anti-VEFG of anti-VEGFR therapies；
The patients with rapid progression of viscera invasion(liver lesion >1/2 viscera area or liver dysfunction);
The patients have uncontrollable mental illness.
The patients who had serious adverse effect to oral vinorelbine or were allergic to vinorelbine.
The patients who have only bone metastasis without other measurable lesion;
The patients experience severe cardiovascular diseases;
The patients experience severe upper gastrointestinal ulcer or malabsorption syndrome.
Abnormal bone marrow functions(neutrophil<1.5G/L, platelet count <75G/L, hemoglobin <90g/L)；
Abnormal renal function(serum creatinine > 1.5 times the upper limit of normal value)；
Abnormal liver function(serum bilirubin ≤ 1.5 times the upper limit of normal value);
The patients have uncontrollable brain metastasis;
The patients do not have good compliance to the therapy.
Facility Information:
Facility Name
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
City
Beijing
State/Province
Beijing
Country
China
12. IPD Sharing Statement
Learn more about this trial
Study of Apatinib Combined With Oral Vinorelbine in Metastatic HER2 Negative Breast Cancer
We'll reach out to this number within 24 hrs