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

Phase 2

Completed

• Conditions: Metastatic Breast Cancer
• Interventions: Drug: WX-671; Drug: placebo

• Registration Number: NCT00615940
• Lead Sponsor: Heidelberg Pharma AG

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2008-02-01
• Study First Submitted QC: 2008-02-01
• Study First Posted: 2008-02-14
• Study Start: 2008-07
• Primary Completion: 2011-12
• Study Completion: 2012-04
• Status Verified: 2014-01
• Disposition First Submitted: 2014-01-28
• Disposition First Submitted QC: 2014-01-28
• Last Update Submitted: 2014-01-28
• Disposition First Posted: 2014-02-28
• Last Update Posted: 2014-02-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 132

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	WX-671	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.
2	placebo	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.

Primary Outcome Measures

Name	Time	Method
Efficacy in terms of progression-free survival (PFS)	disease staging with CT/MRI/bone scans at regular intervals

Secondary Outcome Measures

Name	Time	Method
Secondary endpoints are objective response rate (ORR), overall survival, safety and pharmacokinetics.	2 years

Trial Locations

Locations (20)

AZ Klina, Oncology Department; 🇧🇪 Brasschaat, Belgium

Institut Jules Bordet Oncologie Médicale; 🇧🇪 Bruxelles, Belgium

CHU de Liège, Domaine Universitaire de Sart-Tilman, Oncology Department; 🇧🇪 Liège, Belgium

Davidof Center, Rabin Medical Center, Department of Oncology; 🇮🇱 Petah Tikva, Israel

Kaplan Medical Center, Department of Oncolocy; 🇮🇱 Rehovot, Israel

Sheba Medical Center, Department of Oncology; 🇮🇱 Tel Hashomer, Israel

Assaf Harofeh medical center, Department of Oncology; 🇮🇱 Zerifin, Israel

Instituto Nacional do Câncer - INCA; 🇧🇷 Rio de Janeiro, Brazil

Instituto Brasileiro de Controle do Câncer - IBCC; 🇧🇷 São Paulo, Brazil

Uniklinik Frankfurt, Zentrum der Frauenheilkunde und Geburtshilfe; 🇩🇪 Frankfurt/Main, Germany

Montefiore Medical Center Weiler Division Department; 🇺🇸 New York, New York, United States

Irmandade de Misericórdia da Santa Casa de Porto Alegre; 🇧🇷 Porto Alegre, Brazil

Gemeinschaftspraxis Dr. Brudler, Dr. Heinrich, Dr. Bangerter; 🇩🇪 Augsburg, Germany

Universitätsklinikum der Martin-Luther-Universität Halle-Wittenberg, Poliklinik Gynäkologie; 🇩🇪 Halle/Saale, Germany

Universitätsklinikum Essen, Innere Klinik und Poliklinik (Tumorforschung); 🇩🇪 Essen, Germany

Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Uniklinik Köln; 🇩🇪 Cologne, Germany

Bethesda KH; 🇩🇪 Mönchengladbach, Germany

Universitys Hospital Case Medical Center; 🇺🇸 Cleveland, Ohio, United States

Department of Obstetrics and Gynecology, Technical University; 🇩🇪 Munich, Germany

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States