Clinical trial NCT00615940: Combination of Oral WX-671 Plus Capecitabine vs. Capecitabine Monotherapy in First-line Her2-negative Metastatic Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Keywords: HER2negative
Lead sponsor: Heidelberg Pharma AG
Sponsor class: INDUSTRY
Collaborators: name: U.S. Army Medical Research and Development Command
First posted: 2008-02-14
Enrollment: 132
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Efficacy in terms of progression-free survival (PFS)
timeFrame: disease staging with CT/MRI/bone scans at regular intervals
Secondary outcomes:
measure: Secondary endpoints are objective response rate (ORR), overall survival, safety and pharmacokinetics.
timeFrame: 2 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Montefiore Medical Center Weiler Division Department
state: New York
city: Cleveland
country: United States
facility: Universitys Hospital Case Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Brasschaat
country: Belgium
facility: AZ Klina, Oncology Department
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet Oncologie Médicale
city: Liège
country: Belgium
facility: CHU de Liège, Domaine Universitaire de Sart-Tilman, Oncology Department
city: Porto Alegre
country: Brazil
facility: Irmandade de Misericórdia da Santa Casa de Porto Alegre
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional do Câncer - INCA
city: São Paulo
country: Brazil
facility: Instituto Brasileiro de Controle do Câncer - IBCC
city: Augsburg
country: Germany
facility: Gemeinschaftspraxis Dr. Brudler, Dr. Heinrich, Dr. Bangerter
city: Cologne
country: Germany
facility: Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Uniklinik Köln
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Innere Klinik und Poliklinik (Tumorforschung)
city: Frankfurt/Main
country: Germany
facility: Uniklinik Frankfurt, Zentrum der Frauenheilkunde und Geburtshilfe
city: Halle/Saale
country: Germany
facility: Universitätsklinikum der Martin-Luther-Universität Halle-Wittenberg, Poliklinik Gynäkologie
city: Munich
country: Germany
facility: Department of Obstetrics and Gynecology, Technical University
city: Mönchengladbach
country: Germany
facility: Bethesda KH
city: Petah Tikva
country: Israel
facility: Davidof Center, Rabin Medical Center, Department of Oncology
city: Rehovot
country: Israel
facility: Kaplan Medical Center, Department of Oncolocy
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center, Department of Oncology
city: Zerifin
country: Israel
facility: Assaf Harofeh medical center, Department of Oncology
Study officials:
affiliation: Dept. of Medical Oncology, Division of Medical Science, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, Pennsylvania 19111, USA
name: Lori Goldstein, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Uniklinik Köln
name: Nadia Harbeck, MD
role: PRINCIPAL_INVESTIGATOR
References: