Breast CancerPhase 1NCT01840488
BN83495 Phase I in Post-menopausal Women
A Phase 1 study testing Irosustat (BN83495) in people with Breast Cancer, run by Ipsen at 5 sites in 3 countries.
Trial summary
The purpose of this study is to determine the optimal biological dose (OBD) of Irosustat (BN83495) in postmenopausal women with oestrogen receptor (ER) positive locally advanced or metastatic breast cancer with disease progression after prior hormonal therapy. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Irosustat (BN83495)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 5 sitesin 3 countries
- Study dates
- Apr 2007to Sep 2010
- 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
- Women over the age of 18 whose disease progressed after the first line of hormonal therapy for advanced or metastatic breast cancer.
- Patients with no more than two prior hormonotherapy settings defined as adjuvant and first line of hormonotherapy Or - two lines of hormonotherapy given for advanced or metastatic disease
- Patients with prior adjuvant hormonal therapy who relapse after 12 months of adjuvant treatment.
- Patients with no more than two prior chemotherapy treatments defined as adjuvant and first line of chemotherapy Or two lines of chemotherapy given for advanced or metastatic disease Patients with no more than one prior therapy for Her2 positive breast cancer
- Postmenopausal women, defined as: i) no spontaneous menses for a total of 2 years, ii) amenorrheic for at least 12 months with serum oestrogen level <30 pg/mL, and both LH/FSH >20 IU/L, chemotherapy-induced amenorrhea for at least 12 months, iii) bilateral oophorectomy, or radiation castration and amenorrheic for at least 3 months.
- Histologically or cytologically confirmed breast cancer.
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- Laboratory documentation of ER-positive and/or progesterone receptor(PR) positive status.
- ECOG performance status ≤2.
- Adequate bone marrow function as determined by:
- Haemoglobin >10 g/dL,Neutrophil count of >1.5 x 109 per litre, Platelet count of >75 x 109 per litre
- Satisfactory hepatic function as measured by: serum bilirubin <1.5 ULN and either ALT or AST <2.5 x ULN (<5 x ULN in the presence of liver metastases). Alkaline phosphatase <2.5 ULN in the absence of liver metastases or <5 x ULN in the presence of liver or bone metastases.
- Satisfactory renal function as measured by either a serum creatinine value of <1.5 x ULN or a creatinine clearance ≥60 mL/min.
- Life expectancy of at least 12 weeks.
- Patients with measurable or non-measurable lesions (RECIST criteria)
- Patients included after the Optimal Biological Dose (OBD) is defined must have measurable lesion (RECIST criteria).
Who cannot join
- Patients with progressive central nervous system metastases.
- Patients with inflammatory breast cancer.
- Patients with a marked baseline prolongation of QTc interval (e.g., repeated demonstration of a QTcf interval >450 ms).
- Patients with a history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
- Patients taking concomitant medications that are known to prolong the QTc interval (e.g., antihistamines, quinolones, antipsychotics etc).
- Patients with pre-existing cardiac failure (American Heart Association Grade 3 or 4) or a myocardial infarction within the six months prior to the start of the study.
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- Patients with systolic and diastolic blood pressure below 100 and 60 mmHg respectively.
- Patients with uncontrolled abnormalities of serum potassium, sodium, calcium or magnesium levels.
- Patients with a coexisting significant disease or systemic infection.
- Patients with uncontrolled diabetes (applicable only for the additional six patients included after the OBD is defined).
- Patients who have malabsorption.
- Patients who started biphosphonates therapy within 4 weeks prior to start of this study
- Patients who are taking drugs that inhibit the carbonic anhydrase II (CAII) (e.g. acetazolamide, brinzolamide, dichlorphenamide, dorzolamide, methazolamide).
- Patients who are taking coumarin like drugs (vitamin K antagonists).
- Patients who are incapable of giving informed consent or complying with the protocol.
- Patients who have received previous investigational therapies must have stopped those therapies for at least 4 weeks before treatment with BN83495.
- Patients who have received previous therapy for this cancer within less than 1 month of entry in the study and/or who have received trastuzumab within less than 4 months of entry in the study, and/or fulvestrant within less than 2 months of entry.
- Patients who have a history of hypersensitivity to the IMP or drugs with a similar chemical structure.
- Patients who have a history of, or known current, problems with alcohol abuse.
- Patients who have any mental condition rendering the patients unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude.
- Patients who have abnormal baseline findings, any other medical condition or laboratory findings that, in the opinion of the Investigator, might jeopardise the patients' safety or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
France3 sites
Centre Paul Papin
Angers, 49000
Institut Georges François Leclerc
Dijon, 21079
Centre Eugène Marquis
Rennes, 35042
United Kingdom1 site
Imperial College Healthcare NHS Trust
London, W12 0NN
About this study
Official title: A Phase I Dose Escalation Study To Determine The Optimal Biological Dose Of BN83495 - An Oral Steroid Sulphatase Inhibitor - In Postmenopausal Women With Oestrogen-Receptor Positive Breast Cancer Whose Disease Progressed After Prior Therapy For Locally Advanced/Metastatic Disease
The purpose of this study is to determine the optimal biological dose (OBD) of Irosustat (BN83495) in postmenopausal women with oestrogen receptor (ER) positive locally advanced or metastatic breast cancer with disease progression after prior hormonal therapy.
This study is designed to provide necessary information on safety and dose response of BN83495, when given by repeated once daily oral administration, while achieving a maximal STS inhibition and a maximal reduction in plasma oestradiol (E2) and adiol levels. The data obtained will be used to plan further clinical studies.
- Conditions
- Breast Cancer
- Being tested
- Irosustat (BN83495)
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Irosustat (BN83495)Drug
Three parts (A, B \& C) open label, multiple cohort, dose escalation study with once daily administration of irosustat at 1, 5, 20, 40 and 80 mg. Patients treated in any cohort were not allowed to escalate to higher doses or be enrolled in another dosing cohort.
Part A - Single oral daily dose for 7 days, Part B - Repeated oral daily dose for 28 days and Part C - Repeated oral daily administration until disease progression.
| Study group | Role | What they receive |
|---|---|---|
| Irosustat (BN83495) | Experimental | Single oral administration of irosustat Receives: Drug: Irosustat (BN83495) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in percentage of steroid sulphatase (STS) inhibition in circulating Peripheral Blood Mononuclear Cells (PBMCs) after repeated daily therapy
The combined evaluation of ≥95% STS inhibition in PBMCs relative to Baseline after 7 and 28 days (Day 15 and Day 36,respectively) of continuous treatment and reduction in plasma E2 and adiol levels after 28 days of repeated daily administration, to determine the optimal biological dose (OBD) of irosustat.
Measured: Days 15 and 36
Secondary outcomes (1)
Percentage of steroid sulphatase (STS) inhibition in circulating Peripheral Blood Mononuclear Cells (PBMCs) after a single dose
Measured: Day 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2013 (estimated)
- Study startApr 2007
- Primary completionSep 2010
- Study completionSep 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by IpsenThe 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
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ipsen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director Oncology, Study director, Ipsen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01840488
- Sponsor's protocol ID
- X-55-58064-002
- Other IDs
- 2006-005347-28
- Status last verified
- Nov 2019
- First submitted
- 23 Apr 2013
- Last updated
- 22 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Escalation Study To Determine The Optimal Biological Dose Of BN83495 - An Oral Steroid Sulphatase Inhibitor - In Postmenopausal Women With Oestrogen-Receptor Positive Breast Cancer Whose Disease Progressed After Prior Therapy For Locally Advanced/Metastatic Disease
- ClinicalTrials.gov ID
- NCT01840488
- Acronym / sponsor ID
- X-55-58064-002
- Conditions
- Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- IpsenIndustry (pharma, biotech, devices)
- Study start
- Apr 2007
- Primary completion
- Sep 2010 (actual)
- Study completion
- Sep 2010 (actual)
- First posted
- 25 Apr 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.
The purpose of this study is to determine the optimal biological dose (OBD) of Irosustat (BN83495) in postmenopausal women with oestrogen receptor (ER) positive locally advanced or metastatic breast cancer with disease progression after prior hormonal therapy.
This study is designed to provide necessary information on safety and dose response of BN83495, when given by repeated once daily oral administration, while achieving a maximal STS inhibition and a maximal reduction in plasma oestradiol (E2) and adiol levels. The data obtained will be used to plan further clinical studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Irosustat (BN83495) | Experimental | Drug: Irosustat (BN83495)Single oral administration of irosustat |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Women over the age of 18 whose disease progressed after the first line of hormonal therapy for advanced or metastatic breast cancer.
- Patients with no more than two prior hormonotherapy settings defined as adjuvant and first line of hormonotherapy Or - two lines of hormonotherapy given for advanced or metastatic disease
- Patients with prior adjuvant hormonal therapy who relapse after 12 months of adjuvant treatment.
- Patients with no more than two prior chemotherapy treatments defined as adjuvant and first line of chemotherapy Or two lines of chemotherapy given for advanced or metastatic disease Patients with no more than one prior therapy for Her2 positive breast cancer
- Postmenopausal women, defined as: i) no spontaneous menses for a total of 2 years, ii) amenorrheic for at least 12 months with serum oestrogen level <30 pg/mL, and both LH/FSH >20 IU/L, chemotherapy-induced amenorrhea for at least 12 months, iii) bilateral oophorectomy, or radiation castration and amenorrheic for at least 3 months.
Key exclusion criteria (21 listed)
- Patients with progressive central nervous system metastases.
- Patients with inflammatory breast cancer.
- Patients with a marked baseline prolongation of QTc interval (e.g., repeated demonstration of a QTcf interval >450 ms).
- Patients with a history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
- Patients taking concomitant medications that are known to prolong the QTc interval (e.g., antihistamines, quinolones, antipsychotics etc).
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 |
|---|---|---|
| Irosustat (BN83495)Three parts (A, B \& C) open label, multiple cohort, dose escalation study with once daily administration of irosustat at 1, 5, 20, 40 and 80 mg. Patients treated in any cohort were not allowed to escalate to higher doses or be enrolled in another dosing cohort. Part A - Single oral daily dose for 7 days, Part B - Repeated oral daily dose for 28 days and Part C - Repeated oral daily administration until disease progression. | Drug | Irosustat (BN83495) |
Primary outcome
Change in percentage of steroid sulphatase (STS) inhibition in circulating Peripheral Blood Mononuclear Cells (PBMCs) after repeated daily therapy
Time frame: Days 15 and 36
The combined evaluation of ≥95% STS inhibition in PBMCs relative to Baseline after 7 and 28 days (Day 15 and Day 36,respectively) of continuous treatment and reduction in plasma E2 and adiol levels after 28 days of repeated daily administration, to determine the optimal biological dose (OBD) of irosustat.
1 secondary outcome
Percentage of steroid sulphatase (STS) inhibition in circulating Peripheral Blood Mononuclear Cells (PBMCs) after a single dose
Time frame: Day 8
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 22 Nov 2019.
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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.
Medical Director Oncology study director
Ipsen
5 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Irosustat (BN83495) in people with Breast Cancer, run by Ipsen at 5 sites in 3 countries.
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 15 inclusion and 21 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 22 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 5 sites in France, Belgium, United Kingdom. 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?
Change in percentage of steroid sulphatase (STS) inhibition in circulating Peripheral Blood Mononuclear Cells (PBMCs) after repeated daily therapy (time frame: Days 15 and 36). 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 22 Nov 2019.