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Sorafenib and Fulvestrant in Treating Patients With Locally Advanced or Metastatic Breast Cancer That Did Not Respond to Aromatase Inhibitor Therapy

A Phase II Open-Label Study of Sorafenib Plus Fulvestrant as Salvage Therapy for Hormone Receptor Positive Metastatic Breast Cancer Failing Prior Aromatase Inhibitor Treatment

Status
Terminated
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00722072
Enrollment
12
Registered
2008-07-25
Start date
2008-07-31
Completion date
2012-07-31
Last updated
2018-02-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Cancer

Keywords

male breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, recurrent breast cancer

Brief summary

RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant may fight breast cancer by blocking the use of estrogen by the tumor cells. Giving sorafenib together with fulvestrant may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving sorafenib together with fulvestrant works in treating patients with locally advanced or metastatic breast cancer that did not respond to aromatase inhibitor therapy.

Detailed description

OBJECTIVES: Primary * To investigate the clinical activity of sorafenib tosylate and fulvestrant, as determined by a 4-month progression-free survival rate, in patients with hormone receptor-positive locally advanced or metastatic breast cancer that progressed after prior treatment with an aromatase inhibitor. Secondary * To determine the objective response rate in patients treated with this regimen. * To determine the median time to progression in patients treated with this regimen. * To determine the progression-free survival of patients treated with this regimen. * To determine the overall survival of patients treated with this regimen. * To establish the safety and tolerability profile of this regimen in these patients. OUTLINE: Patients receive oral sorafenib tosylate twice daily on days 1-28. Patients also receive fulvestrant intramuscularly on days 1 and 15 of course 1 and on day 1 of all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 28-56 days.

Interventions

DRUGfulvestrant

Loading dose for cycle 1: 500 mg intramuscular(IM) on Day 1;250 mg IM on Day 15 Upon completion of the loading dose, a fixed dose of fulvestrant 250 mg IM will be administered on day 1 of the next 28 day cycle and every consecutive cycle until tumor progression or until unacceptable toxicity occurs requiring discontinuation of study therapy

DRUGsorafenib tosylate

Subjects will take sorafenib 800 mg/day administered as 400 mg bid (twice daily) each morning and evening approximately 12 hours apart. Treatment will begin on Day 1 of the study and continue daily until tumor progression or until an unacceptable toxicity occurs which would require delay, modification or discontinuation of study therapy

Sponsors

National Cancer Institute (NCI)
CollaboratorNIH
OHSU Knight Cancer Institute
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No

Inclusion criteria

DISEASE CHARACTERISTICS: * Diagnosis of incurable breast cancer * Locally advanced or metastatic disease * Measurable or evaluable disease * Measurable disease is defined as ≥ 1 uni-dimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral computed tomography(CT) scan * Bone-only metastases that can be imaged with bone scan AND magnetic resonance imaging (MRI) or bone scan AND plain x-ray is considered measurable disease * Tumor lesions that are situated in a previously irradiated area are considered measurable only if they are progressing at the time of study entry * Evaluable disease includes unresectable skin/chest wall metastases that can be photographed and whose size can be measured with a ruler * Bone-only metastases that can only be imaged using bone scan or malignant pleural effusion(s) only are not considered evaluable disease * Previously treated with a third-generation aromatase inhibitor (e.g., letrozole, anastrazole, or exemestane) AND meets one of the following criteria: * Progressed during palliative aromatase inhibitor therapy * Recurred during adjuvant aromatase inhibitor therapy * Recurred within 12 months of completing adjuvant aromatase inhibitor therapy * Human Epidermal growth factor Receptor 2(HER2/neu)-negative tumor * No Human Epidermal growth factor Receptor 2(HER2/neu) overexpression (i.e., tumor staining 3+ by immunohistochemistry \[IHC\] or gene amplified by Fluorescence In Situ Hybridization \[FISH\]) * Hormone receptor status: * Estrogen receptor and/or progesterone receptor positive, defined as ≥ 10% of malignant cells with positive nuclear staining PATIENT CHARACTERISTICS: * Postmenopausal * Eastern Cooperative Group(ECOG) performance status 0-1 * Life expectancy ≥ 16 weeks * Neutrophil count ≥ 1,500/mm\^³ * Platelet count ≥ 100,000/mm\^³ * Hemoglobin ≥ 9.0 g/dL * Creatinine \< 2 mg/dL * Total bilirubin ≤ 1.5 times upper limit of normal (ULN) * Alanine aminotransferase (ALT) and aspartate aminotransferase(AST) ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver involvement) * International Normalized Ratio(INR) \< 1.5 OR Prothrombin time/ partial thromboplastin time (PT/PTT) normal * Left ventricular ejection fraction(LVEF) normal by Multiple Gated Acquisition(MUGA) or ECHO * No known allergy to sorafenib tosylate or fulvestrant * No cardiac disease, including any of the following: * New York Heart Association(NYHA) class III-IV congestive heart failure * Unstable angina (anginal symptoms at rest) or new-onset angina (within the past 3 months) * Myocardial infarction within the past 6 months * Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy * No uncontrolled hypertension, defined as systolic blood pressure \> 150 mm Hg or diastolic blood pressure \> 90 mm Hg despite optimal medical management * No thrombotic or embolic events, such as cerebrovascular accident (including transient ischemic attacks), within the past 6 months * No known HIV infection or chronic hepatitis B or C infection * No infection that requires IV antibiotics or produces a fever \> 100°F within the past 72 hours * No pulmonary hemorrhage/bleeding event ≥ Common terminology criteria for adverse events(CTCAE) grade 2 within the past 4 weeks * No other hemorrhage/bleeding event ≥ CTCAE grade 3 within the past 4 weeks * No evidence or history of bleeding diathesis or coagulopathy * No significant traumatic injury within the past 2 weeks * No serious, nonhealing wound, ulcer, or bone fracture * No condition that impairs the patient's ability to swallow whole pills * No malabsorption problem * No second malignancy within the past 5 years, except adequately treated and cured basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * No underlying medical condition that, in the principal investigator's opinion, will make the administration of study drug hazardous or would obscure the interpretation of adverse events PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior chemotherapy for metastatic or unresectable locally advanced breast cancer * No prior sorafenib tosylate or other Vascular endothelial growth factor(VEGF)-targeting therapies * More than 2 weeks since prior major surgery or open biopsy * No concurrent anticoagulation with warfarin or heparin * No concurrent Hypericum perforatum (St. John wort) or rifampin * No other concurrent anticancer agents, including chemotherapy or biological therapy * No other concurrent investigational drugs * Concurrent bisphosphonates allowed

Design outcomes

Primary

MeasureTime frameDescription
Number of Participants With Progression-free Survival at 4 Months4 months after initiating treatment with sorafenib plus fulvestrant.Progression-free survival rate is defined as the proportion of subjects who are progression free (CR, PR and SD) at 4 months after initiating treatment with sorafenib plus fulvestrant. Complete Response (CR):Disappearance of all target (both measurable and evaluable)lesions. Partial Response (PR):At least a 30% decrease in the sum of the longest diameter (LD) of both measurable and evaluable target lesions. Stable Disease (SD):Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease(PD).

Secondary

MeasureTime frame
Objective Response RateEvery 8 weeks (two cycles) while receiving study therapy.
Time to ProgressionStart of treatment to time of progression.
Progression-free SurvivalStart of treatment to time of progression or death, whichever comes first.
Overall Survival28 to 56 days after discontinuation of study therapy

Countries

United States

Participant flow

Participants by arm

ArmCount
Sorafenib and Fulvestrant
Fulvestrant:Will be administered to the subject intramuscularly. Administered to all subjects during cycle 1 of treatment as follows: * 500 mg IM on Day 1 * 250 mg IM on Day 15 Sorafenib: 800 mg/day administered as 400 mg bid (twice daily) each morning and evening approximately 12 hours apart. Treatment will begin on Day 1 of the study and continue daily until tumor progression or until an unacceptable toxicity occurs which would require delay, modification or discontinuation of study therapy.
12
Total12

Baseline characteristics

CharacteristicSorafenib and Fulvestrant
Age, Categorical
<=18 years
0 Participants
Age, Categorical
>=65 years
3 Participants
Age, Categorical
Between 18 and 65 years
9 Participants
Age, Continuous57.166 years
STANDARD_DEVIATION 9.0235
Region of Enrollment
United States
12 participants
Sex: Female, Male
Female
12 Participants
Sex: Female, Male
Male
0 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
9 / 9
serious
Total, serious adverse events
3 / 9

Outcome results

Primary

Number of Participants With Progression-free Survival at 4 Months

Progression-free survival rate is defined as the proportion of subjects who are progression free (CR, PR and SD) at 4 months after initiating treatment with sorafenib plus fulvestrant. Complete Response (CR):Disappearance of all target (both measurable and evaluable)lesions. Partial Response (PR):At least a 30% decrease in the sum of the longest diameter (LD) of both measurable and evaluable target lesions. Stable Disease (SD):Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease(PD).

Time frame: 4 months after initiating treatment with sorafenib plus fulvestrant.

ArmMeasureValue (NUMBER)
Sorafenib and FulvestrantNumber of Participants With Progression-free Survival at 4 Months6 Participants
Secondary

Objective Response Rate

Time frame: Every 8 weeks (two cycles) while receiving study therapy.

Population: Response assessment data was not collected past 4 months due to early study termination.

Secondary

Overall Survival

Time frame: 28 to 56 days after discontinuation of study therapy

Population: Long term survival data was not collected due to early study termination

Secondary

Progression-free Survival

Time frame: Start of treatment to time of progression or death, whichever comes first.

Population: Long term survival data was not collected due to early study termination

Secondary

Time to Progression

Time frame: Start of treatment to time of progression.

Population: Progression data was not collected due to early study termination.

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026