A Study of Famitinib Malate in HER2-negative Metastatic Breast Cancer

A Single-Institutional, Phase II, Open-label, Single Arm Trial of Famitinib Malate in in HER2-negative Metastatic Breast Cancer

The hypothesis of this clinical research study is to discover if the study drug Famitinib Malate can shrink or slow the growth of pretreated HER2-negative metastatic breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Neoplasms
• Intervention / Treatment: Drug: Famitinib Malate

Detailed Description

Famitinib Malate is a tyrosine kinase inhibitor mainly targeting vascular endothelial growth factor receptor 2(VEGFR2), 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 recommended phase II dose is 25 mg. The hypothesis of this clinical research study is to discover if the study drug Famitinib Malate can shrink or slow the growth of pretreated HER2-negative breast cancer. The safety of Famitinib Malate 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 Famitinib Malate is safe and effective in pretreated HER2-negative metastatic breast cancer patients.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • 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.
• Women diagnosed with HER2-negative breast cancer. 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 from the last chemotherapy regimen, but experienced at most 2 regimens in the relapsed or metastatic setting. Pretreated anthracycline, taxanes and capecitabine (any rational reason for no use of capecitabine is acceptable) are mandatory.
• Have failed from at least 1 endocrine therapy, if HR positive.
• 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.
• 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 ≥ 90g/L, 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 ≤ 1.5 x ULN), serum cholesterol ≤ 1.25 x ULN, serum glycerin trilaurate ≤ 2.0 x ULN, LVEF ≥ lower limit of normal (LLN).
• 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 (which include oral contraception, injectable or implantable methods, intrauterine devices, or properly used barrier contraception) from the beginning of the study to 8 weeks after the last dose of the investigated drug. A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives.
• 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.
• Uncontrolled hypertension with mono-drug therapy (>140/90 mm Hg)；ischemia of the myocardium （≥ grade 2） or myocardial infarction；arrhythmia（≥ grade 2, QTcF > 480ms for female patients） or New York Heart Association Class III/IV.
• Abnormal thyroid function history with drug intervention.
• 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.
• Brain or meningeal metastases.
• 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.
• The active HBV or HCV infection or HBV DNA ≥10^4/ml.
• Acquired or inherent immunodeficiency； HIV infection； organ transplantation history.
• Abuse of alcohol or drugs.
• Have received prior treatment with a VEGFR TKI (Bevacizumab is permitted).
• History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix.

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: Famitinib Malate; Famitinib 25mg/d	Drug: Famitinib Malate; The starting dose of Famitinib Malate will be 25 mg/d. Two dose reductions will be allowed to 20 and then 15 mg/d.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
ORR (Objective response rate)	8 Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
PFS(Progression free survival)	8 Weeks
OS (Overall survival)	8 Weeks
CBR(Clinical benefit rate)	8 Weeks
QoL (Quality of life)	8 Weeks
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

• Cao J, Zhang J, Wang Z, Wang B, Lv F, Wang L, Hu X. Hypothyroidism as a potential biomarker of efficacy of famitinib, a novel VEGFR-2 inhibitor in metastatic breast cancer. Cancer Chemother Pharmacol. 2014 Aug;74(2):389-98. doi: 10.1007/s00280-014-2505-x. Epub 2014 Jun 18.

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

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 1, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Metastatic Breast Cancer; HER-2 negative; Famitinib Malate
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: Fudan BR2012-10