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

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Neoplasms
• Intervention / Treatment: Drug: Apatinib

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 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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200032
    • Fudan University Cancer Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apatinib; Apatinib 500mg/d	Drug: Apatinib; The starting dose of apatinib will be 500mg/d. Two dose reductions will be allowed to 375 and then 250 mg/d.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PFS(Progression free survival)	8 Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
ORR (Objective response rate)	8 Weeks
OS (Overall survival)	8 Weeks
CBR(Clinical benefit rate)	8 Weeks
QoL (Quality of life)	8 Weeks
Toxicity (Number of adverse events)	8 Weeks

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: Xi-Chun Hu, Doctor, Fudan Univeristy Cancer Hospital

Publications and helpful links

General Publications

• 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.
• Hu X, Cao J, Hu W, Wu C, Pan Y, Cai L, Tong Z, Wang S, Li J, Wang Z, Wang B, Chen X, Yu H. Multicenter phase II study of apatinib in non-triple-negative metastatic breast cancer. BMC Cancer. 2014 Nov 7;14:820. doi: 10.1186/1471-2407-14-820.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: July 10, 2012
• First Submitted That Met QC Criteria: July 27, 2012
• First Posted (Estimate): July 31, 2012

Study Record Updates

• Last Update Posted (Estimate): December 3, 2013
• Last Update Submitted That Met QC Criteria: December 2, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Apatinib; Metastatic breast cancer; non-triple-negative
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: Fudan BR2012-08