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

Metastatic Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00615940
• Other study ID #: WX/60-006
• Status: Completed
• Phase: Phase 2
• First received: February 1, 2008
• Last updated: January 28, 2014
• Start date: July 2008
• Est. completion date: April 2012

Study information

• Verified date: January 2014
• Source: Wilex
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Federal Institute for Drugs and Medical DevicesBrazil: National Health Surveillance AgencyBelgium: The Federal Public Service (FPS) Health, Food Chain Safety and EnvironmentUkraine: State Pharmacological Center - Ministry of HealthIsrael: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 132
• Est. completion date: April 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• WX-671
capsules taken per os once daily until progression or toxicity
• placebo
capsule taken per os once daily until progression or toxicity

Locations

Country	Name	City	State
Belgium	AZ Klina, Oncology Department	Brasschaat
Belgium	Institut Jules Bordet Oncologie Médicale	Bruxelles
Belgium	CHU de Liège, Domaine Universitaire de Sart-Tilman, Oncology Department	Liège
Brazil	Irmandade de Misericórdia da Santa Casa de Porto Alegre	Porto Alegre
Brazil	Instituto Nacional do Câncer - INCA	Rio de Janeiro
Brazil	Instituto Brasileiro de Controle do Câncer - IBCC	São Paulo
Germany	Gemeinschaftspraxis Dr. Brudler, Dr. Heinrich, Dr. Bangerter	Augsburg
Germany	Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Uniklinik Köln	Cologne
Germany	Universitätsklinikum Essen, Innere Klinik und Poliklinik (Tumorforschung)	Essen
Germany	Uniklinik Frankfurt, Zentrum der Frauenheilkunde und Geburtshilfe	Frankfurt/Main
Germany	Universitätsklinikum der Martin-Luther-Universität Halle-Wittenberg, Poliklinik Gynäkologie	Halle/Saale
Germany	Bethesda KH	Mönchengladbach
Germany	Department of Obstetrics and Gynecology, Technical University	Munich
Israel	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
United States	Universitys Hospital Case Medical Center	Cleveland	Ohio
United States	Montefiore Medical Center Weiler Division Department	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Wilex	U.S. Army Medical Research and Materiel Command

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Germany,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy in terms of progression-free survival (PFS)		disease staging with CT/MRI/bone scans at regular intervals	No
Secondary	Secondary endpoints are objective response rate (ORR), overall survival, safety and pharmacokinetics.		2 years	Yes