BN83495 Phase I in Post-menopausal Women

NCT01840488 | Completed Phase 1

• 2 other identifiers: X-55-58064-0022006-005347-28
• Study Type: interventional
• Target: 50
• Locations: 3 countries
• Sites: 5

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• 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.

  Days 15 and 36

Secondary Outcomes (1)

• Percentage of steroid sulphatase (STS) inhibition in circulating Peripheral Blood Mononuclear Cells (PBMCs) after a single dose

  Day 8

Study Arms (1)

Irosustat (BN83495)

EXPERIMENTAL

Single oral administration of irosustat

Drug: Irosustat (BN83495)

Interventions

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.

Irosustat (BN83495)

Eligibility Criteria

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

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Ipsen: lead

Study Sites (5)

Institut Jules Bordet

Brussels, B- 1000, Belgium

Location

Centre Paul Papin

Angers, 49000, France

Location

Institut Georges François Leclerc

Dijon, 21079, France

Location

Centre Eugène Marquis

Rennes, 35042, France

Location

Imperial College Healthcare NHS Trust

London, W12 0NN, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

irosustat

Condition Hierarchy (Ancestors)

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

Study Officials

• Medical Director Oncology

  Ipsen

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: April 23, 2013
• First Posted: April 25, 2013
• Study Start: April 1, 2007
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: November 22, 2019

Record last verified: 2019-11

Locations

FR (3); GB (1); BE (1)