Post Menopausal, Hormone Receptor Positive Breast CancerPhase 1NCT01808040
A Phase 1b Study of TAK-700 in Postmenopausal Women With Hormone-receptor Positive Metastatic Breast Cancer
A Phase 1 study testing TAK700 in people with Post Menopausal, Hormone Receptor Positive Breast Cancer, run by University of Wisconsin, Madison at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Post Menopausal, Hormone Receptor Positive Breast Cancer
- What is being tested?
- TAK700
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2012to 9 Dec 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- Patients meeting any of the following exclusion criteria are not to be enrolled in the study.
- 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:
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- 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.
- Exclusion Criteria for Dose Expansion Cohort Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
- They are ineligible by virtue of meeting any exclusion criteria above. Patients with known brain metastases will be excluded from this portion of the clinical trial (which will assess PFS and TTP) because of their relatively poor overall prognosis.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
- Being tested
- TAK700
- Keywords
- breast cancer, ER positive, PR positive, post menopausal
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAK700Drug
Also called Orteronel
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: TAK700 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: one year
Secondary outcomes (4)
Overall Response Rate
Determine the overall response rate (ORR) and disease control rate (DCR) for orteronel in all patients treated with orteronel on protocol
Measured: one year
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Determine toxicity of orteronel in patients being treated at the RP2D
Measured: one year
pharmacodynamic activity of orteronel with steroid and endocrine levels
Demonstrate the pharmacodynamic activity of orteronel by assessing steroid hormone and other endocrine levels before and following administration of orteronel.
Measured: two years
response rate, progression-free survival and time to progression
To determine the ORR, DCR, progression-free survival (PFS) and time-to-progression (TTP) in HR+ metastatic breast cancer patients receiving orteronel in the dose-expansion cohort
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2013 (estimated)
- Study startNov 2012
- Primary completionJul 2014
- Study completion9 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post Menopausal, Hormone Receptor Positive Breast CancerStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Amye J Tevaarwerk, MD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01808040
- Sponsor's protocol ID
- CO11109
- Other IDs
- 2012-0355, NCI-2012-02022, A534260, SMPH\MEDICINE\HEM-ONC
- Status last verified
- Sep 2017
- First submitted
- 16 Jan 2013
- Last updated
- 18 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Study of TAK-700 in Postmenopausal Women With Hormone-receptor Positive Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT01808040
- Acronym / sponsor ID
- CO11109
- Keywords
- breast cancer, ER positive, PR positive, post menopausal
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- Nov 2012
- Primary completion
- Jul 2014 (actual)
- Study completion
- 9 Dec 2016 (actual)
- First posted
- 8 Mar 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: TAK700Tak700 (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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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.
Key exclusion criteria (23 listed)
- Patients meeting any of the following exclusion criteria are not to be enrolled in the study.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TAK700Also: Orteroneldose 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 | Drug | 1 |
Primary outcome
Number of Participants with Adverse Events as a Measure of Safety and Tolerability as a way to determine the recommended phase 2 dose.
Time frame: one year
Determine the RP2D of orteronel in postmenopausal women with hormone-receptor positive (HR+) metastatic breast cancer.
decrease in serum estradiol level
Time frame: one year
To demonstrate clinically significant decrease in serum estradiol following treatment with orteronel at RP2D in postmenopausal women with HR+ metastatic breast cancer.
4 secondary outcomes
Overall Response Rate
Time frame: one year
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time frame: one year
pharmacodynamic activity of orteronel with steroid and endocrine levels
Time frame: two years
response rate, progression-free survival and time to progression
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2019.
- University of Wisconsin Carbone Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amye J Tevaarwerk, MD principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TAK700 in people with Post Menopausal, Hormone Receptor Positive Breast Cancer, run by University of Wisconsin, Madison at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Adverse Events as a Measure of Safety and Tolerability as a way to determine the recommended phase 2 dose. (time frame: one year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2019.