A Study of Apatinib in Non-triple-negative Metastatic Breast Cancer

Breast Neoplasms Clinical Trial

Official title:

A Multi-institutional, Open-label, Single Arm Study of Apatinib in Non-triple-negative Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01653561
• Other study ID #: Fudan BR2012-08
• Status: Completed
• Phase: Phase 2
• First received: July 10, 2012
• Last updated: December 2, 2013
• Start date: November 2011
• Est. completion date: October 2012

Study information

• Verified date: August 2013
• Source: Fudan University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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 non-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 non-triple-negative metastatic breast cancer patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

?= 18 and = 70 years of age.

• ECOG performance status of 0-1.

• Metastatic breast cancer, confirmed by histological analysis.

• Have experienced at least 1 and at most 4 regimens, and failed from the last chemotherapy regimen. Pretreated anthracycline, taxanes and capecitabine (any rational reason for no use of capecitabine is acceptable) are mandatory.

• Women diagnosed with human epidermal growth factor receptor positive (HER2+) should have failed for at least 1 anti-HER2 therapy (any rational reason for no use of anti-HER2 therapy is acceptable). HER2+ is defined as +++ staining on immunohistochemistry or FISH/CISH positive for gene amplification.

• Women diagnosed with HR+ should have failed for at least 1 hormonal therapy.

• 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 1.0 criteria that has not been previously irradiated.

• Life expectancy of more than 3 months.

• Negative serum or urine pregnancy test taken in all women within 7 days before inclusion. Sexually active women of childbearing potential must use a medically acceptable form of contraception from the beginning of the study to 8 weeks after the last dose of the investigated drug.

• Written informed consent prior to study specific screening procedures.

Exclusion Criteria:

• Triple-negative breast cancer (ER-, PR- and HER2-. HER2- is defined as 0 or 1+ staining on immunohistochemistry or FISH/CISH negative for gene amplification. )

• Pregnant or lactating women.

• Less than 4 weeks from the last clinical trial.

• Uncontrolled hypertension with mono-drug therapy (>140/90 mm Hg);ischemia of the myocardium (= grade 2) or myocardial infarction;arrhythmia(= grade 2, QTcF > 470ms for female patients) or New York Heart Association Class III/IV

• Any factors that influence the usage of oral administration.

• The cumulative doses of doxorubicin and epirubicin before inclusion have surpassed 300 mg/m2 and 600 mg/m2, respectively.

• Duration from the last therapy (chemotherapy, radiotherapy, target therapy and operation) is less than 4 weeks (Duration for nitroso or mitomycin is less than 6 weeks).

• Confirmed brain metastasis.

• Inadequate hepatic, renal, heart, and hematologic functions (hemoglobin <90g/L, neutrophils < 1.5×10^9/L, platelets < 80×10^9/L , ALT > 2.5 x upper limit of normal (ULN)(5x for liver metastasis), AST > 2.5 x ULN (5x for liver metastasis), serum bilirubin > 1.5 x ULN, serum creatine > 1.0 x ULN, creatinine clearance rate = 50ml/min, LVEF < lower limit of normal (LLN).

• Abnormal coagulative function, inclined to bleeding or is receiving thrombolytictherapy or anticoagulation.

• History of arterial/venous embolic events (such as cerebrovascular accident, TIA, deep vein thrombus,and pulmonary embolism)

• Unhealed wound (> 30 days) 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).

• Acquired or inherent immunodeficiency; HIV infection; organ transplantation history.

• The active HBV or HCV infection or HBV DNA =10^4/ml.

• History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix.

• Presence of serious harm to subjects or complication to hinder the completion of the study judged by investigators

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

Drug:
• Apatinib
The starting dose of apatinib will be 500mg/d. Two dose reductions will be allowed to 375 and then 250 mg/d.

Locations

Country	Name	City	State
China	Fudan University Cancer Hospital	Shanghai	Shanghai
China	Fudan University Cancer Hospital	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Fudan University	Jiangsu HengRui Medicine Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PFS(Progression free survival)		8 Weeks	Yes
Secondary	ORR (Objective response rate)		8 Weeks	Yes
Secondary	CBR(Clinical benefit rate)		8 Weeks	Yes
Secondary	OS (Overall survival)		8 Weeks	Yes
Secondary	QoL (Quality of life)		8 Weeks	Yes
Secondary	Toxicity (Number of adverse events)		8 Weeks	Yes