Combination of Oral WX-671 Plus Capecitabine vs. Capecitabine Monotherapy in First-line Her2-negative Metastatic Breast Cancer

Study Overview
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Brief Summary
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This randomized, double-blind, placebo controlled phase II trial is studying how well capecitabine works when given in combination with WX-671 or when given alone in treating patients receiving first-line therapy for her2negative metastatic breast cancer.

Official Title
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A Phase 2, Two-arm, Double-blind, Multi-center, Randomized Study of the Combination of Oral WX-671 Plus Capecitabine vs. Capecitabine Monotherapy in First-line Her2-negative Metastatic Breast Cancer

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: WX-671
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females aged ≥ 18 years Patients appropriate for palliative first-line, mono chemotherapy with capecitabine Histological or cytological confirmed, non-inflammatory metastatic breast cancer Availability of paraffin-embedded tumor tissue from the primary resection or biopsy of a metastatic lesion. HER2-negative breast cancer Complete staging within 2 weeks prior to randomization (4 weeks for bone scan). Radiologically confirmed disease ECOG performance status of ≤ 2 Ability to understand and willingness to voluntarily sign and date a written informed consent form before screening Negative pregnancy test (urine or serum) within 3 days before first study drug for women of childbearing potential. Use of effective contraception during the study and for 3 months after stopping study drug treatment. 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). 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). Exclusion Criteria: 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). Prior chemotherapy or biologic therapy for metastatic disease. Major surgery within 4 weeks prior to the start of treatment. Other anti-cancer treatment (e.g. hormones) within 2 weeks before the start of treatment. Treatment within 12 months with adjuvant 5-FU containing chemotherapy (regarded as indicating 5-FU resistance) and/or prior capecitabine therapy. Radiation therapy. 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. History of or radiological evidence of brain metastasis including previously treated, resected or asymptomatic brain lesions or leptomeningeal involvement. Active seizure disorder or history of cerebrovascular accident (CVA) or transient ischemic (TI) attack within the past 12 months. History of other malignancy within the last 3 years except for surgically cured non-melanoma skin cancer or cervical carcinoma in situ. Active cardiac disease e.g. unstable angina, congestive heart failure, myocardial infarction (MI) within the preceding 6 months. Any medical condition prohibiting standard imaging procedures Pregnant or breast-feeding. 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. Any surgical or medical condition that might significantly alter the absorption, distribution, metabolism or excretion of either study drug. Known hepatitis B/C or HIV (human immunodeficiency virus) infection.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Capecitabine, 1000 mg/m2, twice daily by mouth, on Days 1 to 14, followed by a 7 day rest in each 21 day cycle given in combination with WX-671 once daily by mouth, Days 1-21 inclusive. | Drug: WX-671<br>* capsules taken per os once daily until progression or toxicity<br>|
| Experimental: 2<br>Capecitabine, 1000 mg/m2, twice daily by mouth, on Days 1 to 14, followed by a 7 day rest in each 21 day cycle given in combination with placebo once daily by mouth, Days 1-21 inclusive. | Drug: placebo<br>* capsule taken per os once daily until progression or toxicity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy in terms of progression-free survival (PFS) |  | disease staging with CT/MRI/bone scans at regular intervals | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary endpoints are objective response rate (ORR), overall survival, safety and pharmacokinetics. |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER2negative