Orteronel as Monotherapy in Patients With Metastatic Breast Cancer (MBC) That Expresses the Androgen Receptor (AR)

NCT01990209 | Completed Phase 2 Results

• 1 other identifier: SCRI BRE 203
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 10

Brief Summary

The androgen receptor (AR) is expressed in 70-90 percent of primary breast tumors and in 75 percent of breast metastases. There is evidence to suggest that Androgen Receptor (AR) may be a target in patients with advanced breast cancer. Breast cancer patients whose tumors do not express the ER, PR or HER2 (triple negative) have very few options for treatment. Orteronel is being developed as an endocrine therapy for relevant hormone-sensitive cancers such as prostrate cancer and breast cancer. Triple-negative metastatic breast cancer patients with AR expression could potentially benefit from anti-androgen therapy like orteronel.

Conditions

Metastatic Breast Cancer

Keywords

triple-negative breast cancer; orteronel; TAK-700; metastatic breast cancer

Outcome Measures

Primary Outcomes (2)

• Response Rate (RR)

  Response rate (RR) will be estimated as the percentage of patients exhibiting complete response or partial response out of all evaluable cases. Complete Response is defined per RECIST as the disappearance of all target/non-target lesions and normalization of tumor markers. Partial Response is defined per RECIST as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Complete and partial responses were confirmed at least 4 weeks after the initial response.

  upto 36 months

• Disease Control Rate (DCR)

  Defined as the percentage of patients who do not exhibit progression (CR+PR+SD) at 6 months among those patients who are evaluable for response by RECIST V1.1. Complete Response is defined per RECIST as the disappearance of all target/non-target lesions and normalization of tumor markers. Partial Response is defined per RECIST as At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Stable disease is defined per RECIST as Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest (nadir) sum LD since the treatment started.

  6 months

Secondary Outcomes (10)

• Number of Participants With Treatment-Related Adverse Events as a Measure of Safety

  weekly for 4 weeks then every 8 weeks until end of study treatment, up to 36 months.

• Progression-free Survival (PFS)

  Every 8 weeks during treatment then every 6 months for 2 years, annually thereafter up to 5 years.

• Overall Survival (OS)

  After disease progression is documented, survival was monitored every 6 months for 2 years and annually thereafter up to 5 years.

• Measurement of Serum Hormone Levels - Estradiol

  At baseline, at day 1 of cycle 2 and 4 (treatment cycle repeated every 4 weeks), and at end of treatment visit, up to 36 months

• Measurement of Serum Hormone Levels - Total Testosterone

  At baseline, at day 1 of cycle 2 and 4 (treatment cycle repeated every 4 weeks), and at end of treatment visit, up to 36 months

Other Outcomes (2)

• Number of Participants With PTEN Gene Expression Status of Positive, Weak Positive, or Negative

  At pre-screening

• Number of Participants With PIK3CA Gene Mutation Status of Mutated or No Mutation

  At pre-screening

Study Arms (1)

Orteronel

EXPERIMENTAL

The planned dose of orteronel is 300mg orally (PO) twice daily (BID), for a total daily dose of 600mg.

Drug: Orteronel

Interventions

Orteronel DRUG

Also known as: Tak-700

Orteronel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care
• 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.
• 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.
• In addition to having AR+ tumors, patients must fit into 1 of the 2 following categories:
• 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.)
• 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.
• Female or male patients ≥18 years-of-age
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
• Patient has recovered (to Grade ≤1) from all clinically significant toxicities related to prior antineoplastic therapies (with the exception of alopecia)
• Adequate hematological function, defined as:
• Absolute neutrophil count (ANC) ≥1.25 x 109/L
• Platelets ≥75 x 109/L
• Hemoglobin ≥9 g/dL
• Adequate liver function, defined as:
• 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

You may not qualify if:

• Known hypersensitivity to orteronel or to orteronel excipients, which are listed by formulation in the Investigator Brochure
• 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.
• Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period.
• Prior anti-androgen therapy
• 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.
• 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.
• Patients with known adrenal insufficiency, or patients receiving treatment with ketoconazole, abiraterone, or aminoglutethimide.
• 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.
• Major surgical procedures ≤28 days of beginning study treatment or minor surgical procedures ≤7 days. No waiting is required following port-a-cath placement.
• 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).
• 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.
• New York Heart Association (NYHA) Class III or IV heart failure
• Electrocardiogram (ECG) abnormalities of Q-wave infarction, unless identified 6 or more months prior to screening or QTc Fridericia (F) interval \>460 msec
• 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.
• 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

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (10)

Yale School of Medicine

New Haven, Connecticut, 06520, United States

Location

Northeast Georgia Medical Center

Gainesville, Georgia, 30501, United States

Location

Hope Cancer Center

Terre Haute, Indiana, 47802, United States

Location

Baptist Hospital East

Louisville, Kentucky, 40207, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Cancer Research Consortium of West Michigan

Grand Rapids, Michigan, 49503, United States

Location

Cancer Centers of SW Oklahoma

Lawton, Oklahoma, 73505, United States

Location

Tennessee Oncology PLLC

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

Center for Cancer and Blood Disorders

Fort Worth, Texas, 76104, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

orteronel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Sarah Cannon Development Innovations, LLC
• Organization: Sarah Cannon Development Innovations, LLC

CANN.InnovationsMedical@sarahcannon.com

844-710-6157

Study Officials

• Howard A Burris, III, MD

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2013
• First Posted: November 21, 2013
• Study Start: March 1, 2014
• Primary Completion: May 1, 2021
• Study Completion: May 1, 2021
• Last Updated: June 30, 2022
• Results First Posted: June 30, 2022

Record last verified: 2022-06

Locations

US (10)