RANDOMIZED, PHASE 3 STUDY OF SUNITINIB IN COMBINATION WITH CAPECITABINE COMPARED WITH CAPECITABINE IN PATIENTS WITH PREVIOUSLY TREATED BREAST CANCER

• Conditions: Advanced/metastatic breast cancer; MedDRA version: 8.1Level: LLTClassification code 10006279Term: Breast neoplasm

• Registration Number: EUCTR2006-004624-36-GR
• Lead Sponsor: Pfizer Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-04-04
• Last Update Posted: 3 September 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 430

Inclusion Criteria

1.Histologically or cytologically proven diagnosis of breast adenocarcinoma with evidence of locally advanced or metastatic disease not amenable to surgery or radiation therapy with curative intent.
2.Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST).
3.Prior treatment with an anthracycline and a taxane in the neoadjuvant, adjuvant or metastatic disease setting
4.Candidate for treatment with capecitabine, not contraindicated according to the local standard of care.
5.Prior treatment with chemotherapy as follows:
•Receipt of adjuvant chemotherapy with RECIST or World Health Organization (WHO)-defined disease progression documented during treatment or disease relapse within 12 months of last treatment, OR
•Receipt of chemotherapy in the first-line advanced disease setting with RECIST or WHO-defined disease progression documented during or, following treatment. Patients entering the study on the basis of this criterion may have also previously received neoadjuvant or adjuvant treatment with chemotherapy.
6.Prior treatment with hormonal therapy as follows:
•Hormonal therapy concurrent or sequential to adjuvant chemotherapy is allowed.
•Hormonal therapy for advanced disease is allowed but is to be discontinued >3 weeks prior to study randomization.
7.Patients with HER2 positive disease (ie, FISH or CISH (where approved) positive or immunohistochemistry +3) may enter the study provided that they have previously received treatment with trastuzumab and where standard of care, lapatinib in the adjuvant or advanced disease setting.
8.May have received prior radiation therapy. A measurable lesion that has been previously irradiated will be evaluated only when it increases in size. Radiotherapy is to be completed >3 weeks prior to study randomization.
9.Female or male, 18 years of age or older.
10.ECOG performance status 0 or 1.
11.Resolution of all acute toxic effects of prior therapy or surgical procedures to grade <1 (except alopecia).
12.Adequate organ function as defined by the following criteria:
•Serum aspartate transaminase (AST) >2.5 x upper limit of normal (ULN) or <5 x ULN if liver function abnormalities are due to underlying malignancy
•Total serum bilirubin <1.5 x ULN regardless of liver involvement secondary to tumor
•Serum albumin >3.0 g/dL
•Serum creatinine <1.5 x ULN
•Creatinine clearance >50 mL/min
•Absolute neutrophil count (ANC) >1500/uL
•Platelets >100,000/uL
•Hemoglobin >9.0 g/dL
•Left ventricular ejection fraction (LVEF) =50% as measured by either multigated acquisition (MUGA) scan or echocardiogram (ECHO)
13.Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment.
14.Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Histology of inflammatory carcinoma.
2.Prior treatment with >2 chemotherapy regimens in the advanced disease setting.
3.Prior treatment with capecitabine.
4.Known hypersensitivity to 5-fluorouracil.
5.Known dihydropyrimidine dehydrogenase deficiency.
6.Major surgery, radiation therapy, or systemic therapy within 3 weeks of study randomization. At least 1 week should elapse since minor surgical procedure including placement of an access device or fine needle aspiration.
7.Prior high-dose chemotherapy requiring hematopoietic stem cell rescue.
8.Prior radiation therapy to >25% of the bone marrow (whole pelvis is 25%).
9.Current treatment on another clinical trial.
10.Brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease.
11.Diagnosis of any second malignancy within the last 3 years, except for adequately treated basal cell carcinoma or squamous cell skin cancer or in situ carcinoma of the cervix uteri.
12.Any of the following within the 12 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack, or pulmonary embolus.
13.Ongoing cardiac dysrhythmias of NCI CTCAE grade >2, atrial fibrillation of any grade, or QTc interval >470 msec for females or >450 msec for males.
14.Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy).
15.Current treatment with therapeutic doses of coumarin-derivative anticoagulants, such as warfarin and phenprocoumon (low dose up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed. If currently receiving treatment patient must have PT or INR <1.5 ULN.
16.Known human immunodeficiency virus infection.
17.Female who is pregnant or nursing; female of child-bearing potential who is unwilling or unable to use adequate contraception to prevent pregnancy during the program All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to randomization.
18.Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: •To demonstrate that the combination of sunitinib plus capecitabine is superior to capecitabine monotherapy in prolonging the progression-free survival (PFS) for ABC patients;Secondary Objective: To compare measures of duration of tumor control and overall survival <br>To compare the safety sunitinib plus capecitabine versus capecitabine monotherapy<br>To compare the patient reported outcomes <br>;Primary end point(s): •Progression-free survival (PFS)