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

NCT01808040 | Completed Phase 1 DMC

• 5 other identifiers: CO111092012-0355NCI-2012-02022A534260SMPH\MEDICINE\HEM-ONC
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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

Keywords

breast cancer; ER positive; PR positive; post menopausal

Outcome Measures

Primary Outcomes (2)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability as a way to determine the recommended phase 2 dose.

  Determine the RP2D of orteronel in postmenopausal women with hormone-receptor positive (HR+) metastatic breast cancer.

  one year

• decrease in serum estradiol level

  To demonstrate clinically significant decrease in serum estradiol following treatment with orteronel at RP2D in postmenopausal women with HR+ metastatic breast cancer.

  one year

Secondary Outcomes (4)

• Overall Response Rate

  one year

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  one year

• pharmacodynamic activity of orteronel with steroid and endocrine levels

  two years

• response rate, progression-free survival and time to progression

  2 years

Other Outcomes (2)

• assess changes in serum estrogen, progesterone, androgen and other hormones

  2 years

• Response to orteronel with AR and ER alpha expression

  2 years

Study Arms (1)

1

EXPERIMENTAL

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

Drug: TAK700

Interventions

TAK700 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

Also known as: Orteronel

1

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Links

• University of Wisconsin Carbone Cancer Center

MeSH Terms

Conditions

Breast Neoplasms

Interventions

orteronel

Condition Hierarchy (Ancestors)

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

Study Officials

• Amye J Tevaarwerk, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2013
• First Posted: March 8, 2013
• Study Start: November 1, 2012
• Primary Completion: July 1, 2014
• Study Completion: December 9, 2016
• Last Updated: November 18, 2019

Record last verified: 2017-09

Locations

US (1)