Status:
COMPLETED
Fulvestrant With or Without Bortezomib in Patients With Inoperable Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer
Lead Sponsor:
National Cancer Institute (NCI)
Conditions:
Metastatic Breast Carcinoma
Stage IIIB Breast Cancer AJCC v7
Eligibility:
FEMALE
18+ years
Phase:
PHASE2
Brief Summary
This randomized phase II trial studies how well fulvestrant works with or without bortezomib in treating patients with estrogen receptor positive breast cancer that has spread to other places in the b...
Detailed Description
PRIMARY OBJECTIVES: I. To determine if the addition of bortezomib to fulvestrant improves median progression free survival (PFS) compared with fulvestrant alone in postmenopausal women with estrogen ...
Eligibility Criteria
Inclusion
- ELIGIBILITY CRITERIA FOR ARM A AND ARM B
- Patients must have histologically or cytologically confirmed ER+ positive breast cancer
- Patients must be postmenopausal, defined as: (1) a history of at least 12 months without spontaneous menstrual bleeding, (2) prior bilateral salpingo-oophorectomy, with or without hysterectomy, (3) age \>= 55 years with a prior hysterectomy with or without oophorectomy, (4) age \< 55 years with a prior hysterectomy without oophorectomy or unknown status, with a documented follicle-stimulating hormone (FSH) level in postmenopausal range within 4 week s of registration, (5) receiving a gonadotropin releasing hormone analog (GnRH) to suppress ovarian function (eg, goserelin 3.6 mg every \[q\] 4 weeks)
- Patients must have stage IV disease or inoperable locally advanced disease
- Patients may have measurable disease only, non-measurable disease only, or both (Response Evaluation Criteria in Solid Tumors \[RECIST 1.1\]); it is anticipated that at least 50% of patients will have only non-measurable disease
- Patients are required to have disease that is resistant to aromatase inhibitor (AI), which is defined either as relapse while receiving adjuvant A.I. therapy (ie, anastrazole, letrozole, or exemestane), and/or disease progression after one or more A.I.s for metastatic disease; prior exposure to more than one AI is permitted
- Patient may have had prior tamoxifen but are not required to
- Patients may have received up to one prior chemotherapy regimen for metastatic disease
- Patients may have received prior bevacizumab
- Patients who have received up to 2 doses of fulvestrant given within a 4 week period prior to registration are eligible; the interval between the first fulvestrant dose and registration must be 6 weeks or less; patients may have received EITHER 250 mg or 500 mg of fulvestrant previously; if the patient has received 250 mg, they will receive the 500 mg loading dose on study day -14; if they already received 500 mg, they will begin the study on day +1
- Life expectancy of greater than 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- Leukocytes \>= 3,000/mcL
- Absolute neutrophil count \>= 1,500/mcL
- Platelets \>= 100,000/mcL
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal
- Creatinine within normal institutional limits OR
- Creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
- Patients must be disease-free of prior invasive malignancies for \>= 5 years with the exception of: curatively-treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix
- Patients must have the ability to understand and the willingness to sign a written informed consent document
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- ELIGIBILITY CRITERIA FOR ARM C
- Previously met all eligibility criteria for arms A and B and registered on trial to arm A (fulvestrant alone)
- Disease progression on arm A and agreeable to crossover to arm C
- Has received no intervening therapy (ie, alternative endocrine therapy, chemotherapy, biologic therapy) between disease progression on arm A and registration an arm C
- ECOG performance status 0-2
- Tumor measurements (eg, computed tomography \[CT\] scan of chest/abdomen/pelvis) within 4 weeks of registration to arm C
- Leukocytes \>= 3,000/mcL, within 2 weeks of registration on arm C
- Absolute neutrophil count \>= 1,500/mcL, within 2 weeks of registration on arm C
- Platelets \>= 100,000/mcL, within 2 weeks of registration on arm C
- Total bilirubin within normal institutional limits, within 2 weeks of registration on arm C
- AST(SGOT)/ALT(SGPT) =\< 2.5 x institutional upper limit of normal, within 2 weeks of registration on arm C
- Creatinine within normal institutional limits, within 2 weeks of registration on arm C OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal, within 2 weeks of registration on arm C
Exclusion
- EXCLUSION CRITERIA FOR ARM A AND ARM B
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients may not be receiving any other investigational agents
- Patients with known brain metastases should be excluded from this clinical trial
- Presence of rapidly progressive, life-threatening metastases; this includes patients with extensive hepatic involvement (\> 50% of the liver involved), symptomatic lymphangitic metastases, or brain or leptomeningeal involvement
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to bortezomib or fulvestrant
- Patients who are concomitantly receiving bortezomib and drugs that are inhibitors or inducers of cytochrome P450 3A4 should be closely monitored for either toxicities or reduced efficacy
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
- Patients who have previously received fulvestrant
- Patients who have previously received bortezomib
- Concomitant anticancer treatment with the following exceptions: (1) bisphosphonates for bone metastases, (2) a GnRH analog is permitted if the patient had progressive disease on a GnRH analog plus a selective estrogen receptor modulators (SERMs) or an AI; the GnRH analog may continue but the SERM or AI must be discontinued
- Grade 2 or more peripheral neuropathy
Key Trial Info
Start Date :
May 26 2010
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
January 8 2021
Estimated Enrollment :
118 Patients enrolled
Trial Details
Trial ID
NCT01142401
Start Date
May 26 2010
End Date
January 8 2021
Last Update
November 27 2023
Active Locations (21)
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1
University of Connecticut
Farmington, Connecticut, United States, 06030
2
Yale University
New Haven, Connecticut, United States, 06520
3
Cleveland Clinic-Weston
Weston, Florida, United States, 33331
4
Washington University School of Medicine
St Louis, Missouri, United States, 63110