Vorinostat in Treating Patients With Stage IV Breast Cancer Receiving Hormone Therapy
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| ClinicalTrials.gov Identifier: NCT01720602 |
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Recruitment Status :
Completed
First Posted : November 2, 2012
Results First Posted : November 6, 2014
Last Update Posted : January 7, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Male Breast Cancer Recurrent Breast Cancer Stage IV Breast Cancer | Drug: vorinostat Drug: anastrozole Drug: letrozole Drug: exemestane Procedure: positron emission tomography Radiation: F-18 16 alpha-fluoroestradiol Radiation: fludeoxyglucose F 18 Other: laboratory biomarker analysis | Not Applicable |
PRIMARY OBJECTIVES:
I. Estimate the rate of clinical benefit (objective response plus stable disease) for patients treated with 28-day cycles of vorinostat (first 5 consecutive days each week for day 1-21) concurrent with daily aromatase inhibitor (AI) therapy (all 28 days).
SECONDARY OBJECTIVES:
I. Assess the safety and tolerability of vorinostat and AI combination therapy in patients with metastatic breast cancer.
II. Assess the change in estrogen receptor (ER) expression, measured as the change in F-18 16 alpha-fluoroestradiol (FES) standardized uptake value (SUV) using FES positron emission tomography (PET) completed per protocol 7184 after two weeks of vorinostat and AI therapy and after 8 weeks of therapy.
III. Assess tumor metabolic response, measured as the change in fludeoxyglucose F 18 (FDG) SUV using FDG PET completed per protocol 7184 after two weeks of vorinostat and AI therapy and after 8 weeks of therapy.
IV. Assess the change in hormone levels (estradiol, estrone, follicle-stimulating hormone [FSH], sex binding globulin, testosterone, and free testosterone) after 8 weeks of therapy.
V. Assess the change in ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), androgen receptor (AR), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) tumor expression after two weeks of vorinostat and AI therapy in patients that consent to optional tissue biopsy procedure.
VI. Assess the time to progression and the overall survival of patients treated with 28-day cycles of vorinostat (first 5 consecutive days each week for day 1-21) concurrent with daily AI therapy (all 28 days).
OUTLINE:
Patients receive vorinostat orally (PO) 5 days a week for 3 weeks. Patients also receive AI therapy comprising either anastrozole PO daily, letrozole PO daily, or exemestane PO daily for 4 weeks. Courses repeat every 28 days in the absence of disease progression and unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months until progression, and then annually thereafter.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 15 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Pilot Study of Vorinostat to Restore Sensitivity to Aromatase Inhibitor Therapy Part B |
| Study Start Date : | November 2012 |
| Actual Primary Completion Date : | March 2015 |
| Actual Study Completion Date : | January 2020 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Treatment (vorinostat, AI therapy)
Patients receive vorinostat PO 5 days a week for 3 weeks. Patients also receive AI therapy comprising either anastrozole PO daily, letrozole PO daily, or exemestane PO daily for 4 weeks. Courses repeat every 28 days in the absence of disease progression and unacceptable toxicity.
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Drug: vorinostat
Given PO
Other Names:
Drug: anastrozole Given PO
Other Names:
Drug: letrozole Given PO
Other Names:
Drug: exemestane Given PO
Other Names:
Procedure: positron emission tomography Correlative studies
Other Names:
Radiation: F-18 16 alpha-fluoroestradiol Correlative studies
Other Names:
Radiation: fludeoxyglucose F 18 Correlative studies
Other Names:
Other: laboratory biomarker analysis Correlative studies |
- Rate of Clinical Benefit of Patients Receiving Vorinostat/AI Combination Therapy According to RECIST [ Time Frame: 8 weeks ]
A 90% score (Wilson) confidence interval will be computed for the rate of clinical benefit.
Clinical benefit according to Recist score is defined as: Stable Disease, Partial Remission or Complete Remission. Lack of clinical benefit is defined as Progressive Disease (increase in target lesion size by 20% or more).
- Response Rate According to RECIST [ Time Frame: 8 weeks ]
A 90% score (Wilson) confidence interval will be computed for the response rate.
Clinical benefit according to Recist score is defined as: Stable Disease, Partial Remission or Complete Remission. Lack of clinical benefit is defined as Progressive Disease (increase in target lesion size by 20% or more).
- Duration of Response [ Time Frame: Up to 5 years ]Duration of response will be summarized for responders.
- Progression-free Survival (PFS) [ Time Frame: From the time of start of study therapy to documented progression - up to 5 years ]Progression-free survival is assessed relative to the start of the study therapy. Progression can be determined by RECIST 1.1, elevated tumor markers, worsening clinical symptoms or new lesions identified by FDG-PET or bone scan.
- Overall Survival [ Time Frame: From the time of start of study therapy to date of documented death ]Overall survival is assessed relative to the start of the study therapy to the date of death, from any cause.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Histologically or cytologically proven diagnosis of breast cancer
- Stage IV disease
- Patient has previously derived clinical benefit from endocrine therapy, but is no longer deriving benefit to endocrine therapy in the opinion of the treating investigator
- At least one site of measurable disease, as defined by the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Female patient is post menopausal as defined by one of the following; free from menses for >= 2 years, surgically sterilized, FSH and estradiol in post-menopausal range AND surgical absence of uterus OR chemotherapy induced amenorrhea lasting > 1 year OR currently on ovarian suppression
- Female patient of childbearing potential has a negative urine or serum (beta human chorionic gonadotropin [B-hCG]) pregnancy test within 14 days prior to receiving the first dose of vorinostat
- Male patient agrees to use two barrier methods of contraception or abstain from intercourse for the duration of the study
- Absolute neutrophil count (ANC) >= 1,500/mcL
- Platelets >= 50,000/mcL
- Hemoglobin >= 9 g/dL
- Prothrombin time or international normalized ratio (INR) =< 1.5 x upper limit of normal (ULN) unless receiving therapeutic anticoagulation
- Partial thromboplastin time (PTT) =< 1.2 times the ULN unless the patient is receiving therapeutic anticoagulation
- Potassium (K) levels normal limits
- Magnesium (Mg) levels normal limits
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Calculated creatinine clearance >= 30 mL/min
- Creatinine clearance should be calculated per institutional standard
- Serum total bilirubin =< 1.5 x ULN
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x ULN
- Alkaline phosphatase =< 2.5 x ULN
- Patient, or the patient's legal representative, has voluntarily agreed to participate by giving written informed consent
- Patient has a life expectancy of at least 12 weeks in the opinion of the treating investigator
- Patient is willing to continue on same AI therapy
- Patient agrees to participate in imaging protocol 7184 and is separately consented
Exclusion Criteria:
- Patient has not derived clinical benefit from prior endocrine therapy
- Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of initial dosing with study drug(s) other than the imaging protocol 7184
- Patient has received an ER blocking therapy (selective estrogen receptor modulating or downregulating selective estrogen receptor modulator [SERM] or selective estrogen receptor degrader [SERD] i.e. tamoxifen or fulvestrant) within the past 6 weeks
- Patient had prior treatment with an histone deacetylase (HDAC) inhibitor (e.g., romidepsin [Depsipeptide], NSC-630176, MS 275, LAQ-824, belinostat (PXD-101), LBH589, MGCD0103, CRA024781, etc); patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study; patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period
- Patient is on any systemic steroids that have not been stabilized to the equivalent of =< 10 mg/day prednisone during the 30 days prior to the start of the study drugs
- Patient has known hypersensitivity to the components of study drug or its analogs
- Patients with uncontrolled brain metastases
- New York Heart Association (NYHA) class III or IV congestive heart failure, myocardial infarction within the previous 6 months, QTc > 0.47 seconds, or uncontrolled arrhythmia
- Type I diabetes mellitus; patients with type II diabetes mellitus will be included as long as their glucose can be controlled to under 200 mg/dL
- Patient is pregnant or breast feeding, or expecting to conceive or father children within the projected duration of the study
- Patient with a "currently active" second malignancy, other than non-melanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled; patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for > 5 years or are considered by their physician to be at less than 30% risk of relapse
- Patients with known active viral hepatitis
- Patient has a history or current evidence of any condition, therapy, or laboratory (lab) abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study or is not in the best interest of the patient to participate
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01720602
| United States, Washington | |
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | |
| Seattle, Washington, United States, 98109 | |
| Principal Investigator: | Hannah Linden | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
| Responsible Party: | University of Washington |
| ClinicalTrials.gov Identifier: | NCT01720602 |
| Other Study ID Numbers: |
7841 NCI-2012-02004 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) P30CA015704 ( U.S. NIH Grant/Contract ) |
| First Posted: | November 2, 2012 Key Record Dates |
| Results First Posted: | November 6, 2014 |
| Last Update Posted: | January 7, 2020 |
| Last Verified: | January 2020 |
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Breast Neoplasms Breast Neoplasms, Male Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Letrozole Anastrozole Vorinostat Exemestane Fluorodeoxyglucose F18 Antineoplastic Agents |
Aromatase Inhibitors Steroid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Estrogen Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antineoplastic Agents, Hormonal Histone Deacetylase Inhibitors Radiopharmaceuticals |