Clinical trial NCT01176669: Study of Apatinib in Metastatic Triple-Negative Breast Cancer Patients
Official title: A Single-Institutional Phase IIa Trial and A Multi-Institutional Phase IIb Trial of Apatinib in Metastatic Triple-Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Keywords: Apatinib
Triple-Negative Breast Cancer
Metastatic Breast Cancer
ER/PR Negative
Her2/Neu Negative
Lead sponsor: Fudan University
Sponsor class: OTHER
Collaborators: name: Jiangsu HengRui Medicine Co., Ltd.
First posted: 2010-08-06
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The hypothesis of this clinical research study is to discover if the study drug apatinib can shrink or slow the growth of pretreated metastatic triple-negative breast cancer.

Detailed description: Apatinib is a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR), and its anti-angiogenesis effect has been viewed in preclinical tests. The investigators' phase I study has shown that the drug's toxicity is manageable and the maximum tolerable daily dose is 850 mg. The hypothesis of this clinical research study is to discover if the study drug apatinib can shrink or slow the growth of triple-negative breast cancer. The safety of apatinib 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 apatinib is safe and effective in pretreated metastatic triple-negative breast cancer patients.

Eligibility criteria: Inclusion Criteria:

* ≥ 18 and ≤ 70 years of age.
* ECOG performance status of 0-1.
* Women diagnosed with triple negative breast cancer (breast cancer is estrogen receptor negative (ER-), progesterone receptor negative (PgR-) and human epidermal growth factor receptor negative (HER2-). HER2- is defined as 0 or 1+ staining on immunohistochemistry or FISH/CISH negative for gene amplification.
* Metastatic breast cancer, confirmed by histological analysis.
* Have failed for at least one chemotherapy regimen, but at most three regimens(including adjuvant and neo-adjuvant setting).
* Duration from the last therapy (chemotherapy, radiotherapy, target therapy and operation) is more than 4 weeks (Duration for nitroso or mitomycin is 6 weeks).
* Have at least one extracranial measurable site of disease according to RECIST 1.1 criteria that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of disease progression since the radiation.
* Life expectancy of more than 3 months.
* If the patients have brain or meninges metastases, the lesions must have been controlled at least 8 weeks.
* Adequate hepatic, renal, heart, and hematologic functions (hemoglobin ≥ 9.0g/dl, neutrophils ≥ 1.5×10\^9/L, platelets ≥ 80×10\^9/L , ALT ≤ 2.5 x upper limit of normal (ULN), AST ≤ 2.5 x ULN, serum bilirubin ≤ 1.5 x ULN, serum creatine ≤ 1.5 x ULN, creatinine clearance rate ≥ 50ml/min, PT, APTT, TT, Fbg normal).
* Written informed consent prior to study specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time without prejudice.

Exclusion Criteria:

* Pregnant or lactating women.
* Less than 4 weeks from the last clinical trial.
* Have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: Congestive heart failure: New York Heart Association Class III/IV, Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease.
* Any factors that influence the usage of oral administration.
* Receiving the therapy of thrombolysis or anticoagulation.
* Unhealed wound or bone fracture.
* Urine protein ≥++ and confirmed \>1.0 g by the 24h quantity.
* Previous or present history of pulmonary fibrosis,interstitial pneumonia,pneumoconiosis,radiation pneumonitis,drug-related pneumonitis or greatly-impaired pulmonary function.
* Disability of serious uncontrolled intercurrence infection.
* Abuse of alcohol or drugs.
* Have received prior treatment with a VEGFR, PDGFR or s-SRC TKI (Bevacizumab is permitted).
* History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix.

Primary outcomes:
measure: DCR(Disease control rate) for IIa
timeFrame: 8 Weeks
measure: PFS(Progression free survival) for IIb
timeFrame: 8 Weeks
Secondary outcomes:
measure: PFS(Progression free survival) for IIa
timeFrame: 8 Weeks
measure: OS (Overall survival)
timeFrame: 8 Weeks
measure: ORR (Objective response rate)
timeFrame: 8 Weeks
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: 8 weeks
measure: QoL (Quality of life)
timeFrame: 8 Weeks
measure: DCR(Disease control rate) for IIb
timeFrame: 8 Weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Cancer Hospital
state: Shanghai
Study officials:
affiliation: Fudan University
name: Xichun Hu, Doctorship
role: STUDY_CHAIR
References:
citation: Fan M, Zhang J, Wang Z, Wang B, Zhang Q, Zheng C, Li T, Ni C, Wu Z, Shao Z, Hu X. Phosphorylated VEGFR2 and hypertension: potential biomarkers to indicate VEGF-dependency of advanced breast cancer in anti-angiogenic therapy. Breast Cancer Res Treat. 2014 Jan;143(1):141-51. doi: 10.1007/s10549-013-2793-6. Epub 2013 Dec 1.