A Phase 1b Study of TAK-700 in Postmenopausal Women With Hormone-receptor Positive Metastatic Breast Cancer

NCT ID: NCT01808040

Last Updated: 2019-11-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2016-12-09

Brief Summary

In this study the investigators want to find out about the effects of this drug in women with metastatic breast cancer. The study has two major parts; dose escalation and dose expansion. In the first part or dose escalation, subjects will be treated at the lowest dose effective in men: 300 mg two times daily. Orteronel (TAK-700) will be increased to reach the highest dose tolerated in men: 400 mg two times daily. This part of the study is designed to see if female subjects can safely tolerate orteronel (TAK-700), and to measure the changes in estrogens and androgens at different levels of TAK-700.

In the second part of the study (dose expansion), seven women will be treated with the dose identified in the first part of the study as being safest and most effective. In this part of the study, the investigators want to see if orteronel (TAK-700) will routinely and significantly decrease the estrogen levels at the dose which will be used for any future studies.

Conditions

Post Menopausal, Hormone Receptor Positive Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Tak700 (orteronel) dose escalation schedule:

• 1a 200 mg PO BID TAK700
• 1b 200mg PO BID TAK + glucocorticoid

1a 300mg PO BID TAK700 starting dose

1b 300 mg po BID + glucocorticoid 2a 400mg PO BID TAK700 2b 400 mg po BID + glucocorticoid

Group Type: EXPERIMENTAL

TAK700

Intervention Type: DRUG

dose is dependant on dose escalation timepoint and dose expansion cohort dose will be the RP2D determined based on the dose escalation cohort final dose recommendation

Interventions

TAK700

dose is dependant on dose escalation timepoint and dose expansion cohort dose will be the RP2D determined based on the dose escalation cohort final dose recommendation

Intervention Type: DRUG

Other Intervention Names

Orteronel

Eligibility Criteria

Inclusion Criteria

• Voluntary written informed consent
• Patients 18 years or older
• Screening clinical laboratory values as specified below:
• Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be the upper limit of normal (ULN).
• Total bilirubin ≤ 1.5 x ULN.
• Serum creatinine ≤ 1.5 × ULN or Estimated creatinine clearance using the Cockcroft-Gault formula must be greater than 50 mL/minute
• Absolute neutrophil count (ANC) greater than 1000/L and platelet count greater than 75,000/L.
• Serum potassium levels must be within institutional normal limits.
• Serum magnesium and phosphorous levels must be ≥ the institutional lower limit of normal.
• Screening calculated ejection fraction greater than or equal to the institutional upper limit of normal
• Patients must have histologically confirmed breast cancer that is Metastatic OR Incurable and locally advanced
• Patients must have histologically confirmed HR+ breast cancer.
• Patients must have measureable or evaluable disease
• ECOG performance status <2 (Karnofsky >60%)
• Patients must be postmenopausal women.

• All of the criteria listed in above in addition to those below:
• Patients must have measurable disease.
• Patients may not have received more than 1 prior line of endocrine therapy in the metastatic setting.
• Patients may not have received any cytotoxic chemotherapy for treatment in the metastatic setting.

Exclusion Criteria

• Patients who have not discontinued all prior medical therapy for breast cancer (with the exception of bisphosphonates or denosumab) at least 28 days prior to first dose of orteronel.
• Patients who are taking any form of other exogenous hormonal therapy within 28 days prior to first dose of orteronel.
• Patients should not have received radiotherapy within 14 days prior to the first dose of orteronel.
• Patients should have recovered to baseline or < grade 1 for all-prior treatment related toxicities.
• EKG abnormalities of:

• Q-wave infarction, unless identified 6 or more months prior to screening QTc interval > 470 msec, the upper limit of normal for women.
• Known hypersensitivity to compounds related to orteronel or to orteronel excipients.
• Uncontrolled hypertension despite appropriate medical therapy
• Known 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.
• Likely inability to comply with the protocol or cooperate fully with the investigator and site personnel.
• Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption or tolerance of orteronel, including difficulty or inability to swallow tablets.
• Patients with known endocrine disorders including, but not limited to, Cushing's, or Addison's disease.
• Patients with known brain metastases are excluded unless they have had definitive treatment (e.g. whole brain radiotherapy or surgery or stereotactic radiation) for brain metastases with evidence of stable/improved disease on repeat imaging following definitive treatment.
• Patients on medications with the potential for significant interaction with orteronel.
• Patients with serious medical illness
• Patients with an estimated life expectancy of less than 3 months as determined by the treating physician.
• Prior therapy with abiraterone, or aminoglutethimide.

• Patients with HER2+ breast cancer are also excluded from this portion of the study as HER2-targeted therapy would generally be considered appropriate for the HER2+ patient population meeting the entry criteria for the dose expansion cohort.
• They have received treatment with orteronel or another lyase inhibitor in the past.
• Diagnosed or treated for another malignancy within 2 years of enrollment, with the exception of in situ malignancies.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amye J Tevaarwerk, MD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

Related Links

https://cancer.wisc.edu/

University of Wisconsin Carbone Cancer Center

Other Identifiers

2012-0355

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2012-02022

Identifier Type: REGISTRY

Identifier Source: secondary_id

A534260

Identifier Type: OTHER

Identifier Source: secondary_id

SMPH\MEDICINE\HEM-ONC

Identifier Type: OTHER

Identifier Source: secondary_id

CO11109

Identifier Type: -

Identifier Source: org_study_id