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

• ClinicalTrials.gov Identifier: NCT00615940
• Recruitment Status: Completed
• First Posted: February 14, 2008
• Last Update Posted: February 28, 2014
• Sponsor: Heidelberg Pharma AG
• Collaborator: U.S. Army Medical Research and Development Command
• Information provided by (Responsible Party): Heidelberg Pharma AG

Tracking Information

• First Submitted Date: February 1, 2008
• First Posted Date: February 14, 2008
• Last Update Posted Date: February 28, 2014
• Study Start Date: July 2008
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 1, 2008): Efficacy in terms of progression-free survival (PFS) [ Time Frame: disease staging with CT/MRI/bone scans at regular intervals ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: February 1, 2008): Secondary endpoints are objective response rate (ORR), overall survival, safety and pharmacokinetics. [ Time Frame: 2 years ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Metastatic Breast Cancer

Intervention

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

Study Arms

• 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.
  Intervention: Drug: WX-671
• 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.
  Intervention: Drug: placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 17, 2012): 132
• Original Estimated Enrollment (submitted: February 1, 2008): 100
• Actual Study Completion Date: April 2012
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Brazil, Germany, Israel, United States
• Removed Location Countries: Ukraine

Administrative Information

• NCT Number: NCT00615940
• Other Study ID Numbers: WX/60-006
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Heidelberg Pharma AG
• Original Responsible Party: Dr. Carola Mala, Wilex
• Current Study Sponsor: Heidelberg Pharma AG
• Original Study Sponsor: Same as current
• 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

• PRS Account: Heidelberg Pharma AG
• Verification Date: January 2014