Phase III Trial Comparing Capecitabine in Combination with Sorafenib or Placebo in the Treatment of Locally Advanced or Metastatic HER2-Negative Breast Cancer

Phase 1

• Conditions: ocally advanced or metastatic HER2-negative breast cancer.; MedDRA version: 19.0Level: LLTClassification code 10004244Term: Benign breast neoplasm NOSSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-018501-10-CZ
• Lead Sponsor: Bayer AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-01-05
• Last Update Posted: 13 June 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 519

Inclusion Criteria

•Age is =18 years.
•Life expectancy is at least 12 weeks (3 months).
•Subject has histologically or cytologically confirmed HER2-negative adenocarcinoma of the breast. HER2 status should be determined by an accredited laboratory by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), or chromogenic in situ hybridization (CISH). Note: local accreditation is acceptable.
•Subject has locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent (Stage IIIb or IIIc; American Joint Committee on Cancer [AJCC] Staging System, Sixth Edition).
•Subject has measurable or non-measurable (but radiologically evaluable) disease (according to RECIST 1.1).
•All computer tomography [CT] [with contrast] and magnetic resonance imaging [MRI]) used to document disease must have been done = 4 weeks before randomization. Bone scans (if clinically indicated) must be done = 12 weeks prior to randomization.
•Subject must have received up to two prior chemotherapy regimens (adjuvant/neo adjuvant treatments are considered one regimen), and no more than one prior regimen for advanced and/or metastatic disease. Chemotherapy regimens include both targeted and biologic therapy.
•Prior regimens must have included an anthracycline (eg, doxorubicin, epirubicin) and a taxane (eg, paclitaxel, docetaxel), either in combination or in separate regimens, in either the neo-adjuvant/adjuvant or the metastatic setting or both, as either monotherapy or as part of a combination with another agent. Sequential regimens will count as a single regimen; multiple neo-adjuvant / adjuvant regimens will count as a single regimen.
•Subject must meet at least one of the following scenarios to be eligible for the study (see Appendix 14.19 in the protocol for definitions of treatment resistance and failure):
-Resistant to or have failed prior taxane and anthracycline
OR
-Resistant to or have failed prior taxane AND for whom further anthracycline therapy is not indicated (eg, intolerance or cumulative doses of doxorubicin or doxorubicin equivalents [eg, epirubicin]).
NOTE: No minimum dose of prior anthracycline or anthracycline equivalents is required.
•Subjects who relapse beyond 12 months after the last taxane or anthracycline dose given in the adjuvant, neo-adjuvant, or metastatic setting are eligible. Further therapy with the agent(s) for a subsequent regimen must have been considered and ruled out for example due to: prior toxicity, intolerance, or local standard of practice (see Appendix 14.19 in the protocol for definitions of treatment intolerance).
•Single agent experimental (not approved) chemotherapy is not allowed. Prior experimental chemotherapy treatment is allowed, provided it is given in combination with at least one drug approved for the treatment of breast cancer (excluding drugs that target VEGF or VEGFR, eg, bevacizumab, brivanib, sunitinib, vatalinib).
•Subject must have discontinued prior chemotherapy, including both targeted and biologic therapies, prior therapeutic radiation therapy, or prior hormonal therapy for locally advanced or metastatic disease = 4 weeks (28 days) before randomization. Start of study treatment is allowed within less than 28 days of the prior therapy provided that 5 half-lives of the prior treatment drug(s) have elapsed before randomization. Previously radiated areas must not be the only site of disease, unless the site had subsequent evidence of progression. Pa

Exclusion Criteria

•HER2-positive breast cancer (IHC = 3+, positive FISH, or positive CISH); equivocal or unknown HER2 status. Subjects with equivocal HER2 status may consent to having their HER2 status retested prior to enrollment by an accredited laboratory.
•Unknown hormone receptor status (estrogen and progesterone receptor).
•No prior taxane and anthracycline for the treatment of breast cancer (either in adjuvant, neo-adjuvant or metastatic setting).
•Bilateral breast cancer or a history of two distinct breast cancers are excluded.
•Inflammatory breast carcinoma are excluded.
•Subject must NOT have
oactive or clinically significant cardiac disease.
othrombotic, embolic, venous, or arterial events within 6 months before randomization.
oany hemorrhage/bleeding event of NCI-CTCAE v4.0 Grade 3 or above within 4 weeks before randomization.
•Radiation to any lesions < 4 weeks prior to randomization. Palliative radiation to bone metastasis for pain control is permitted with provisions.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified