A PHASE 2, TWO-ARM, DOUBLE-BLIND, MULTICENTER, RANDOMIZEDSTUDY OF THE COMBINATION OF ORAL WX-671 PLUS CAPECITABINE VS.CAPECITABINE MONOTHERAPY IN FIRST-LINE HER2-NEGATIVEMETASTATIC BREAST CANCER

• Conditions: Metastatic Breast Cancer (MBC); MedDRA version: 13.1Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2007-006078-27-BE
• Lead Sponsor: Wilex AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-05-07
• Last Update Posted: 7 October 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 140

Inclusion Criteria

1)Females aged = 18 years.
2)Patients appropriate for palliative first-line, mono chemotherapy with capecitabine
3)Histological or cytological confirmed, non-inflammatory metastatic breast cancer
4)Availability of paraffin-embedded tumor tissue from the primary resection or biopsy of a metastatic lesion.
5)HER2-negative breast cancer (as per immunohistochemistry DAKO score 0 1; DAKO score 2 and negative FISH assay; all negative FISH assays).
6)Complete staging within 2 weeks prior to randomization (4 weeks for bone scan).
7)Radiologically confirmed disease: at least one measurable lesion according to RECIST-patients with bone metastases only are allowed
8)ECOG (Eastern Cooperative Oncology Group) performance status of = 2.
9)Ability to understand and willingness to voluntarily sign and date a written informed consent form before screening, following an explanation of the nature and purpose of this study.
10)Negative pregnancy test (urine or serum) within 3 days before first study drug for women of childbearing potential. Effective contraception must be used by women of childbearing potential during the study and for 3 months after stopping study drug treatment.
11)Normal organ and marrow function as defined by laboratory parameters (obtained within the screening period) within the following limits:
•neutrophils >= 1.5 x 109/L;
•platelets >= 100 x 109/L;
•hemoglobin >= 9.0 g/dL (5.6 mmol/L).
Note: Patients may receive blood transfusions as medically appropriate during the study. Patients who require a blood transfusion during screening must have stable hemoglobin (= 9.0 g/dL) without the need for further transfusions during the 2 weeks before first dose of study medication in order to remain eligible;
•total bilirubin <= 1.5 x upper limit of normal (ULN);
•aspartate aminotransferase (AST)/ALT <= 2.5 x ULN (<= 5.0 x ULN for patients with liver metastases);
•serum creatinine <= 2 x ULN, or calculated creatinine clearance >45 mL/min according to Cockroft and Gault formula).

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)Endocrine therapy completed within 2 weeks before the start of treatment (i.e. previous hormone therapy is allowed provided that there is a washout period of 2 weeks).
2)Prior chemotherapy or biologic therapy for metastatic disease.
3)Major surgery within 4 weeks prior to the start of treatment.
4)Other anti-cancer treatment (e.g. hormones) within 2 weeks before the start of treatment.
5)Treatment within 12 months with adjuvant 5-FU containing chemotherapy (regarded as indicating 5-FU resistance) and/or prior capecitabine therapy.
6)Radiation therapy for the metastatic disease. Palliative radiation of stable, non-target lesions more than 2 weeks before the start of treatment is allowed, provided patients have recovered from the radiation side-effects.
7)History of or radiological evidence of brain metastasis including previously treated, resected or asymptomatic brain lesions or leptomeningeal involvement.
8)Active seizure disorder or history of cerebrovascular accident (CVA) or transient ischemic (TI) attack within the past 12 months.
9)History of other malignancy within the last 3 years except for surgically cured non-melanoma skin cancer or cervical carcinoma in situ.
10)Active cardiac disease e.g. unstable angina, congestive heart failure, myocardial infarction (MI) within the preceding 6 months.
11)Any medical condition prohibiting standard imaging procedures
12)Pregnant or breast-feeding.
13)Any unrelated illness, e.g. active infection requiring parenteral antibiotics, inflammation, medical condition or laboratory abnormalities, which in the judgment of the investigator might significantly affect patients’ study participation.
14)Any surgical or medical condition that might significantly alter the absorption, distribution, metabolism or excretion of either study drug.
15)Known hepatitis B/C or HIV (human immunodeficiency virus) infection.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of the combination of WX-671 and capecitabine<br>compared to capecitabine monotherapy, as assessed by comparison of<br>progression free survival rates.;Secondary Objective: To evaluate efficacy in terms of overall survival rates.<br>To compare objective response rates.<br>To compare the safety and tolerability of the combination of WX-671 and<br>capecitabine compared to capecitabine monotherapy.<br>To assess the pharmacokinetics (PK) of WX-671 in this population, and to<br>evaluate the PK of capecitabine when administered with WX-671.;Primary end point(s): Determination of progression-free survival (PFS) following the combination of WX-671 and capecitabine vs. capecitabine monotherapy. PFS refers to the probability that a patient will remain alive, without the disease getting worse. A PFS event is defined as the time from randomization until objective tumor progression or death, whichever is first.