Recruitment

Recruitment Status
Completed
Estimated Enrollment
86

Inclusion Criterias

Willingness and ability to understand the nature of this study and to comply with the study and follow-up procedures.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x the upper limit of normal (ULN), if no liver involvement or ≤5 x ULN with liver involvement
Patients with breast tumors that are AR+ (≥10% staining by immunohisto-chemistry). Archived tumor tissue from a primary biopsy or metastatic lesion for centralized determination of AR expression is mandatory. If tissue is limited, the additional correlative testing is optional. If tissue is not available, a patient will not be eligible for enrollment into the study. Patients may enroll based on local laboratory AR assessment, but will need to submit tissue for confirmation at the central laboratory.
...
Willingness and ability to understand the nature of this study and to comply with the study and follow-up procedures.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x the upper limit of normal (ULN), if no liver involvement or ≤5 x ULN with liver involvement
Patients with breast tumors that are AR+ (≥10% staining by immunohisto-chemistry). Archived tumor tissue from a primary biopsy or metastatic lesion for centralized determination of AR expression is mandatory. If tissue is limited, the additional correlative testing is optional. If tissue is not available, a patient will not be eligible for enrollment into the study. Patients may enroll based on local laboratory AR assessment, but will need to submit tissue for confirmation at the central laboratory.
Male patients (even those post vasectomy) who are willing to use adequate contraceptive measures or abstain from heterosexual intercourse during the entire study treatment period and for 4 months after the last dose of study drug
Female or male patients ≥18 years-of-age
Triple negative (ER-/PR-/HER2-) (Note: This group of patients must have received at least 1 and up to 3 prior chemotherapy regimens in the advanced setting.)
Voluntary written informed consent before performance of any study-related procedure not part of normal medical care
Absolute neutrophil count (ANC) ≥1.25 x 109/L
Platelets ≥75 x 109/L
ER+ and/or PR+ (Note: This group of patients must have received at least 1 and up to 3 prior hormonal therapies and at least one prior chemotherapy treatment in the advanced setting. HER2+ patients in this group must have received a minimum of 2 lines of HER2-directed therapy in the advanced setting.) This group of patients may be pre-menopausal with ovarian suppression or post-menopausal. LHRH agonists maybe used to render ovarian suppression with post-menopausal ranges of estradiol or FSH per institutional guidelines.
Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
Hemoglobin ≥9 g/dL
Ability to swallow and retain oral medication
Total bilirubin ≤1.5 times the upper limit of normal (ULN) (in patients with known Gilbert Syndrome, a total bilirubin ≤3.0 x ULN, with direct bilirubin ≤1.5 x ULN)
Patient has recovered (to Grade ≤1) from all clinically significant toxicities related to prior antineoplastic therapies (with the exception of alopecia)
Screening calculated LVEF of ≥50% by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan
Creatinine ≤1.5 x ULN or creatinine clearance ≥40 mL/min as calculated by the Cockcroft-Gault method
Life expectancy of ≥3 months
Patients must have MBC that is measurable or evaluable as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Patients with metastases limited to the bones are eligible.
Female patients who are not of child-bearing potential and female patients of child-bearing potential who agree to use adequate contraceptive measures or abstain from heterosexual intercourse during the entire study treatment period and for 4 months after the last dose of study drug, who are not breastfeeding, and who have had a negative serum/urine pregnancy test ≤7 days prior to dosing

Exclusion Criterias

Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (eg, ulcerative disease, uncontrolled nausea, vomiting, diarrhea ≥ Grade 2, and malabsorption syndrome).
Major surgical procedures ≤28 days of beginning study treatment or minor surgical procedures ≤7 days. No waiting is required following port-a-cath placement.
Electrocardiogram (ECG) abnormalities of Q-wave infarction, unless identified 6 or more months prior to screening or QTc Fridericia (F) interval >460 msec
...
Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (eg, ulcerative disease, uncontrolled nausea, vomiting, diarrhea ≥ Grade 2, and malabsorption syndrome).
Major surgical procedures ≤28 days of beginning study treatment or minor surgical procedures ≤7 days. No waiting is required following port-a-cath placement.
Electrocardiogram (ECG) abnormalities of Q-wave infarction, unless identified 6 or more months prior to screening or QTc Fridericia (F) interval >460 msec
Use of an investigational drug ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of orteronel, or concurrent treatment. For investigational drugs for which 5 half-lives is less than 21 days, a minimum of 10 days between termination of the investigational drug and administration of orteronel is required.
Uncontrolled diabetes mellitus. Patients with Type II diabetes are eligible if they require only oral hypoglycemic agents and fasting blood glucose level is ≤120. Patients with Type I diabetes are eligible if their glycosylated hemoglobin (HbAlc) is ≤7.
Active brain metastases or leptomeningeal disease. Previously treated brain metastases are allowed provided lesions are stable for at least 3 months as documented by head CT scan or magnetic resonance imaging (MRI) of the brain. Patients must be off steroids, but anti-convulsants are allowed.
Use of a prohibited concomitant medication that cannot be safely discontinued or substituted.
History of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias > Grade 2 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], Version 4.0), thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (eg, pericardial effusion restrictive cardiomyopathy) within 6 months prior to first dose of study drug. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.
Inability or unwillingness (including psychological, familial, sociological, or geographical conditions) to comply with study and/or follow-up procedures as outlined in the protocol.
Prior anti-androgen therapy
Patients with known adrenal insufficiency, or patients receiving treatment with ketoconazole, abiraterone, or aminoglutethimide.
Patients receiving other treatment for breast cancer (includes standard hormonal therapy, chemotherapy, biologic therapy, immunotherapy, or radiation therapy). Patients receiving chronic bisphosphonate or denosumab therapy are eligible.
Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy.
Known diagnosis of human immunodeficiency virus, active chronic hepatitis B, or C, life-threatening illness unrelated to cancer, or any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with participation in this study
New York Heart Association (NYHA) Class III or IV heart failure
Diagnosis or treatment for another malignancy within 2 years of enrollment, with the exception of adequately treated in-situ carcinoma of the cervix, uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer
Known hypersensitivity to orteronel or to orteronel excipients, which are listed by formulation in the Investigator Brochure
Inadequately controlled hypertension (ie, systolic blood pressure [SBP] >160 mmHg or diastolic BP [DBP] >90 mmHg) at 2 separate measurements no more than 60 minutes apart during the Screening visit. Note: patients may be rescreened after adjustment of antihypertensive medications.
Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period.

Summary

Conditions
Metastatic Breast Cancer
Type
Interventional
Phase
Phase 2
Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Both males and females

Description

This open-label multicenter study will be conducted in 2 stages. Lead-in Phase: The first 6 patients treated will be evaluated to confirm the safety and feasibility of this regimen. After all 6 patients complete at least 4 weeks of treatment, and if no prohibitive toxicities are identified, continuo...

This open-label multicenter study will be conducted in 2 stages. Lead-in Phase: The first 6 patients treated will be evaluated to confirm the safety and feasibility of this regimen. After all 6 patients complete at least 4 weeks of treatment, and if no prohibitive toxicities are identified, continuous study treatment will begin. Continuous Study Treatment: Patients will continue to be enrolled into both cohorts based on their tumor specificities with a total of 31 patients in Cohort 1 (ER-/PR-/HER2-/AR+) and 55 patients in Cohort 2 (ER+ and/or PR+/AR+). Patients will be evaluated every eight weeks for response to treatment. All patients who respond to treatment (complete response [CR] or partial response [PR]) or have stable disease (SD) will continue to receive orteronel until they develop progressive disease (PD) or unacceptable toxicity.

Inclusion Criterias

Willingness and ability to understand the nature of this study and to comply with the study and follow-up procedures.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x the upper limit of normal (ULN), if no liver involvement or ≤5 x ULN with liver involvement
Patients with breast tumors that are AR+ (≥10% staining by immunohisto-chemistry). Archived tumor tissue from a primary biopsy or metastatic lesion for centralized determination of AR expression is mandatory. If tissue is limited, the additional correlative testing is optional. If tissue is not available, a patient will not be eligible for enrollment into the study. Patients may enroll based on local laboratory AR assessment, but will need to submit tissue for confirmation at the central laboratory.
...
Willingness and ability to understand the nature of this study and to comply with the study and follow-up procedures.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x the upper limit of normal (ULN), if no liver involvement or ≤5 x ULN with liver involvement
Patients with breast tumors that are AR+ (≥10% staining by immunohisto-chemistry). Archived tumor tissue from a primary biopsy or metastatic lesion for centralized determination of AR expression is mandatory. If tissue is limited, the additional correlative testing is optional. If tissue is not available, a patient will not be eligible for enrollment into the study. Patients may enroll based on local laboratory AR assessment, but will need to submit tissue for confirmation at the central laboratory.
Male patients (even those post vasectomy) who are willing to use adequate contraceptive measures or abstain from heterosexual intercourse during the entire study treatment period and for 4 months after the last dose of study drug
Female or male patients ≥18 years-of-age
Triple negative (ER-/PR-/HER2-) (Note: This group of patients must have received at least 1 and up to 3 prior chemotherapy regimens in the advanced setting.)
Voluntary written informed consent before performance of any study-related procedure not part of normal medical care
Absolute neutrophil count (ANC) ≥1.25 x 109/L
Platelets ≥75 x 109/L
ER+ and/or PR+ (Note: This group of patients must have received at least 1 and up to 3 prior hormonal therapies and at least one prior chemotherapy treatment in the advanced setting. HER2+ patients in this group must have received a minimum of 2 lines of HER2-directed therapy in the advanced setting.) This group of patients may be pre-menopausal with ovarian suppression or post-menopausal. LHRH agonists maybe used to render ovarian suppression with post-menopausal ranges of estradiol or FSH per institutional guidelines.
Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
Hemoglobin ≥9 g/dL
Ability to swallow and retain oral medication
Total bilirubin ≤1.5 times the upper limit of normal (ULN) (in patients with known Gilbert Syndrome, a total bilirubin ≤3.0 x ULN, with direct bilirubin ≤1.5 x ULN)
Patient has recovered (to Grade ≤1) from all clinically significant toxicities related to prior antineoplastic therapies (with the exception of alopecia)
Screening calculated LVEF of ≥50% by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan
Creatinine ≤1.5 x ULN or creatinine clearance ≥40 mL/min as calculated by the Cockcroft-Gault method
Life expectancy of ≥3 months
Patients must have MBC that is measurable or evaluable as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Patients with metastases limited to the bones are eligible.
Female patients who are not of child-bearing potential and female patients of child-bearing potential who agree to use adequate contraceptive measures or abstain from heterosexual intercourse during the entire study treatment period and for 4 months after the last dose of study drug, who are not breastfeeding, and who have had a negative serum/urine pregnancy test ≤7 days prior to dosing

Exclusion Criterias

Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (eg, ulcerative disease, uncontrolled nausea, vomiting, diarrhea ≥ Grade 2, and malabsorption syndrome).
Major surgical procedures ≤28 days of beginning study treatment or minor surgical procedures ≤7 days. No waiting is required following port-a-cath placement.
Electrocardiogram (ECG) abnormalities of Q-wave infarction, unless identified 6 or more months prior to screening or QTc Fridericia (F) interval >460 msec
...
Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (eg, ulcerative disease, uncontrolled nausea, vomiting, diarrhea ≥ Grade 2, and malabsorption syndrome).
Major surgical procedures ≤28 days of beginning study treatment or minor surgical procedures ≤7 days. No waiting is required following port-a-cath placement.
Electrocardiogram (ECG) abnormalities of Q-wave infarction, unless identified 6 or more months prior to screening or QTc Fridericia (F) interval >460 msec
Use of an investigational drug ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of orteronel, or concurrent treatment. For investigational drugs for which 5 half-lives is less than 21 days, a minimum of 10 days between termination of the investigational drug and administration of orteronel is required.
Uncontrolled diabetes mellitus. Patients with Type II diabetes are eligible if they require only oral hypoglycemic agents and fasting blood glucose level is ≤120. Patients with Type I diabetes are eligible if their glycosylated hemoglobin (HbAlc) is ≤7.
Active brain metastases or leptomeningeal disease. Previously treated brain metastases are allowed provided lesions are stable for at least 3 months as documented by head CT scan or magnetic resonance imaging (MRI) of the brain. Patients must be off steroids, but anti-convulsants are allowed.
Use of a prohibited concomitant medication that cannot be safely discontinued or substituted.
History of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias > Grade 2 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], Version 4.0), thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (eg, pericardial effusion restrictive cardiomyopathy) within 6 months prior to first dose of study drug. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.
Inability or unwillingness (including psychological, familial, sociological, or geographical conditions) to comply with study and/or follow-up procedures as outlined in the protocol.
Prior anti-androgen therapy
Patients with known adrenal insufficiency, or patients receiving treatment with ketoconazole, abiraterone, or aminoglutethimide.
Patients receiving other treatment for breast cancer (includes standard hormonal therapy, chemotherapy, biologic therapy, immunotherapy, or radiation therapy). Patients receiving chronic bisphosphonate or denosumab therapy are eligible.
Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy.
Known diagnosis of human immunodeficiency virus, active chronic hepatitis B, or C, life-threatening illness unrelated to cancer, or any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with participation in this study
New York Heart Association (NYHA) Class III or IV heart failure
Diagnosis or treatment for another malignancy within 2 years of enrollment, with the exception of adequately treated in-situ carcinoma of the cervix, uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer
Known hypersensitivity to orteronel or to orteronel excipients, which are listed by formulation in the Investigator Brochure
Inadequately controlled hypertension (ie, systolic blood pressure [SBP] >160 mmHg or diastolic BP [DBP] >90 mmHg) at 2 separate measurements no more than 60 minutes apart during the Screening visit. Note: patients may be rescreened after adjustment of antihypertensive medications.
Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period.

Locations

Gainesville, Georgia, 30501
Nashville, Tennessee, 37203
Grand Rapids, Michigan, 49503
Louisville, Kentucky, 40207
New Haven, Connecticut, 06520
...
Gainesville, Georgia, 30501
Nashville, Tennessee, 37203
Grand Rapids, Michigan, 49503
Louisville, Kentucky, 40207
New Haven, Connecticut, 06520
Bethesda, Maryland, 20817
Fort Worth, Texas, 76104
Lawton, Oklahoma, 73505
Terre Haute, Indiana, 47802
Chattanooga, Tennessee, 37404

Tracking Information

NCT #
NCT01990209
Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Chair: Howard A Burris, III, MD SCRI Development Innovations, LLC