Breast Cancer
Conditions
Keywords
breast cancer, Sorafenib, Nexavar, Endocrine Therapy
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.
Interventions
DRUGsorafenib
400 mg PO (orally) twice daily for 12 months from study enrollment or until disease progression, whichever occurs first.
Sponsors
Bayer
Suleiman Massarweh
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression | continuously | — |
| 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. |
Countries
United States
Participant flow
Recruitment details
11 patients were recruited from the University of Kentucky Markey Cancer Center from November 2009-November 2011.
Participants by arm
| Arm | Count |
|---|---|
| Sorafenib & Endocrine Therapy Sorafenib & Endocrine Therapy
sorafenib: 400 mg PO (orally) twice daily for 12 months from study enrollment or until disease progression, whichever occurs first. | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Sorafenib & Endocrine Therapy |
|---|---|
| Age, Continuous | 45 years |
| Age, Customized 40-49 years | 3 participants |
| Age, Customized <40 years | 3 participants |
| Age, Customized 50-59 years | 1 participants |
| Age, Customized 60-69 years | 2 participants |
| Age, Customized >=70 years | 2 participants |
| Bone metastases No | 2 participants |
| Bone metastases Yes | 9 participants |
| Disease status at entry Progressive Disease | 8 participants |
| Disease status at entry Stable disease with maximal response | 3 participants |
| Endocrine therapy at study entry Anastrozole | 1 participants |
| Endocrine therapy at study entry Exemestane | 1 participants |
| Endocrine therapy at study entry Fulvestrant | 1 participants |
| Endocrine therapy at study entry Letrozole | 1 participants |
| Endocrine therapy at study entry Tamoxifen | 7 participants |
| Estrogen receptor status Negative | 0 participants |
| Estrogen receptor status Positive | 11 participants |
| Human epidermal growth factor receptor 2 (HER2) status Negative | 9 participants |
| Human epidermal growth factor receptor 2 (HER2) status Unknown | 2 participants |
| Line of current endocrine therapy First-line (Primary) treatment | 9 participants |
| Line of current endocrine therapy Second-line (Subsequent) treatment | 2 participants |
| Locally advanced No | 6 participants |
| Locally advanced Yes | 5 participants |
| Lung Metastases No | 6 participants |
| Lung Metastases Yes | 5 participants |
| Prior chemotherapy No | 8 participants |
| Prior chemotherapy Yes | 3 participants |
| Progesterone receptor status Negative | 2 participants |
| Progesterone receptor status Positive | 9 participants |
| Relapsed versus de novo metastasis de novo | 7 participants |
| Relapsed versus de novo metastasis Relapsed | 4 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 11 / 11 |
| serious Total, serious adverse events | 2 / 11 |
Outcome results
Primary
Response Rate
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.
Time frame: 12 weeks after treatment & 8 weeks after initial documentation of response
Population: one discontinued treatment after 2 weeks owing to a grade 3 rash and was not evaluable for response
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sorafenib & Endocrine Therapy | Response Rate | Stable Disease | 7 participants |
| Sorafenib & Endocrine Therapy | Response Rate | Progression | 3 participants |
Comparison: Based on known historical response rate to sorafenib of no better than 5-10%, the study was designed to test the null hypothesis that the clinical response rate is no better than 10% versus the alternative hypothesis that it is at least 25% when sorafenib is added to endocrine therapy. In the first stage, 18 patients were planned for enrollment, and if two or fewer responses were observed, the trial would be terminated. The study stopped after 11 due to slow accrual and withdrawal of funding.
Secondary
Clinical Benefit Rate
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 frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sorafenib & Endocrine Therapy | Clinical Benefit Rate | 50 percentage of participants |
Secondary
Time to Progression
Time frame: continuously
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib & Endocrine Therapy | Time to Progression | 6.1 months |
95% CI: [2.6, 11.3]