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

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: WX-671; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 132
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brasschaat, Belgium, 2930
    • AZ Klina, Oncology Department
  • Bruxelles, Belgium, 1000
    • Institut Jules Bordet Oncologie Médicale
  • Liège, Belgium, 4000
    • CHU de Liège, Domaine Universitaire de Sart-Tilman, Oncology Department
• Brazil
  • Porto Alegre, Brazil, 9005
    • Irmandade de Misericórdia da Santa Casa de Porto Alegre
  • Rio de Janeiro, Brazil, 20560
    • Instituto Nacional do Cancer - INCA
  • São Paulo, Brazil, 03102
    • Instituto Brasileiro de Controle do Cancer - ibcc
• Germany
  • Augsburg, Germany, 86150
    • Gemeinschaftspraxis Dr. Brudler, Dr. Heinrich, Dr. Bangerter
  • Cologne, Germany
    • Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Uniklinik Köln
  • Essen, Germany, 45147
    • Universitätsklinikum Essen, Innere Klinik und Poliklinik (Tumorforschung)
  • Frankfurt/Main, Germany, 60590
    • Uniklinik Frankfurt, Zentrum der Frauenheilkunde und Geburtshilfe
  • Halle/Saale, Germany, 06120
    • Universitätsklinikum der Martin-Luther-Universität Halle-Wittenberg, Poliklinik Gynäkologie
  • Munich, Germany, 81675
    • Department of Obstetrics and Gynecology, Technical University
  • Mönchengladbach, Germany, 41061
    • Bethesda KH
• Israel
  • Petah Tikva, Israel, 49100
    • Davidof Center, Rabin Medical Center, Department of Oncology
  • Rehovot, Israel, 76100
    • Kaplan Medical Center, Department of Oncolocy
  • Tel Hashomer, Israel, 52621
    • Sheba Medical Center, Department of Oncology
  • Zerifin, Israel, 70300
    • Assaf Harofeh medical center, Department of Oncology
• United States
  • New York
    • New York, New York, United States, 10461
      • Montefiore Medical Center Weiler Division Department
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Universitys Hospital Case Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; 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; capsules taken per os once daily until progression or toxicity
Experimental: 2; 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; capsule taken per os once daily until progression or toxicity

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Heidelberg Pharma AG
• Collaborators: U.S. Army Medical Research and Development Command
• Investigators: Principal Investigator: Lori Goldstein, MD, Dept. of Medical Oncology, Division of Medical Science, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, Pennsylvania 19111, USA; Principal Investigator: Nadia Harbeck, MD, Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Uniklinik Köln

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: February 1, 2008
• First Submitted That Met QC Criteria: February 1, 2008
• First Posted (Estimate): February 14, 2008

Study Record Updates

• Last Update Posted (Estimate): February 28, 2014
• Last Update Submitted That Met QC Criteria: January 28, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: HER2negative
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: WX/60-006