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

Sponsor

Heidelberg Pharma AG (Industry)

Overall Status

Completed

CT.gov ID

NCT00615940

Collaborator

U.S. Army Medical Research and Development Command (U.S. Fed)

132

Enrollment

Locations

Arms

Duration (Months)

6.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: WX-671 Drug: placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

132 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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 Start Date :

Jul 1, 2008

Actual Primary Completion Date :

Dec 1, 2011

Actual Study Completion Date :

Apr 1, 2012

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Secondary endpoints are objective response rate (ORR), overall survival, safety and pharmacokinetics. [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

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

Sponsors and Collaborators

Heidelberg Pharma AG
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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Heidelberg Pharma AG

ClinicalTrials.gov Identifier:

NCT00615940

Other Study ID Numbers:

WX/60-006

First Posted:

Feb 14, 2008

Last Update Posted:

Feb 28, 2014

Last Verified:

Jan 1, 2014

Keywords provided by Heidelberg Pharma AG

HER2negative

Additional relevant MeSH terms:

Breast Neoplasms

Study Results

No Results Posted as of Feb 28, 2014