Study Adding Multikinase Inhibitor Sorafenib to Existing Endocrine Therapy in Patients With Advanced Breast Cancer

Phase 2

Terminated

Brief Summary: The purpose of this study is to determine the clinical response rate to sorafenib when added to existing endocrine therapy in patients with advanced breast cancer.

Detailed Description: A pilot Phase II study adding sorafenib to endocrine therapy in 11 patients with metastatic estrogen receptor-positive breast cancer was conducted. Primary end point was response by Response Evaluation Criteria in Solid Tumors (RECIST) after 3 months of sorafenib. Secondary end points included safety, time to progression and biomarker modulation. The study closed early owing to slow accrual.

Recruitment & Eligibility

Inclusion Criteria

All subjects must be female.
Age ≥ 18 years old.
Histologically proven carcinoma of the breast.
Estrogen receptor and/or Progesterone positive disease.
Metastatic or locally advanced disease.
Patients on a preexisting endocrine agent for at least 3 months before enrollment.
Have residual measurable disease after
1. maximal response to endocrine therapy or
2. no response to endocrine therapy or
3. progressive non-visceral disease on endocrine therapy.
Must be able to provide a tumor block from either the primary or metastatic site, if available.
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
Adequate organ function.

Exclusion Criteria

Patients with rapidly progressive disease on endocrine therapy who would otherwise be candidates for chemotherapy.
Other coexisting malignancies, with the exception of basal cell carcinoma or cervical carcinoma in situ.
Prior use of anti-angiogenic agents.
As judged by the investigator, uncontrolled intercurrent illness.
Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
Treatment with a non-approved or investigational drug within 30 days before Day 1 of study treatment.
Concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, or St John's Wort.
Known or suspected allergy to sorafenib or any agent given in the course of this trial.
A serious non-healing wound or ulcer.
Evidence or history of bleeding diathesis or coagulopathy.
Major surgery, open biopsy or significant traumatic injury within the 4 weeks prior to the first dose of the study drug.
Pulmonary hemorrhage/bleeding event ≥ Common Toxicity Criteria for Adverse Effects (CTCAE) Grade 2 within the 4 weeks prior to the first dose of study drug.
Pregnancy
Any condition that impairs patient's ability to swallow whole pills.
Documented malabsorption problem.

Arm && Interventions

Group	Intervention	Description
Sorafenib & Endocrine Therapy	sorafenib	Sorafenib \& Endocrine Therapy

Primary Outcome Measures

Name	Time	Method
Response Rate	12 weeks after treatment & 8 weeks after initial documentation of response	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Patients were followed monthly for clinical and toxicity evaluation. Disease response by RECIST criteria v1.0 was assessed after 3 months by appropriate scans and these were obtained every 2 months thereafter until progression.

Secondary Outcome Measures

Name	Time	Method
Clinical Benefit Rate	24 weeks	Clinical benefit rate is defined as complete response, partial response, or stable disease (CR/PR/SD) as measured by Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for a minimum of at least 24 weeks.
Time to Progression	continuously