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A Phase II, Open Label, Preoperative Study to Assess the Efficacy of the Novel Steroid Sulfatase Inhibitor Irosustat in Postmenopausal Women With Early Oestrogen Receptor Positive Breast Cancer


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Female
Breast Neoplasms

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Trial Information

A Phase II, Open Label, Preoperative Study to Assess the Efficacy of the Novel Steroid Sulfatase Inhibitor Irosustat in Postmenopausal Women With Early Oestrogen Receptor Positive Breast Cancer


Objectives

Primary:

To assess changes in [18F] fluorothymidine (FLT) uptake using Positron Emission Tomography
(PET) following 2 weeks of Irosustat treatment in patients with early, treatment naïve,
oestrogen receptor positive (ER +ve) breast cancer

Secondary:

To assess the:

1. Pharmacodynamic profile of Irosustat

2. Safety and tolerability of Irosustat

Study Population: Postmenopausal women with early, treatment naïve, ER +ve breast cancer


Inclusion Criteria:



1. Written informed consent to participate in the trial

2. 18 years of age or older

3. Histologically confirmed ER +ve breast cancer (Allred ≥ 3)

4. Any HER2 status

5. Tumour measuring ≥ 20mm in longest diameter on ultrasound (US) examination

6. Postmenopausal women as defined by any one of the following criteria:

- Amenorrhoea > 12 months at the time of diagnosis and an intact uterus OR,

- prior bilateral oophorectomy OR,

- FSH levels within the postmenopausal range (as per local practice) in women aged
< 55years who have undergone hysterectomy OR,

- FSH levels within the postmenopausal range (as per local practice) in women aged
< 55 years who have been on Hormone Replacement Therapy (HRT) within the last 12
months and are therefore not amenorrhoeic

7. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

8. Adequate bone marrow function defined by Hb ≥ 10 g/dl, WBC ≥ 3.0 x109, PLT ≥ 100
x109/L. Adequate renal function defined by a serum creatinine ≤ 1.5 x ULN. Adequate
liver function defined by total bilirubin ≤ 1.5 ULN (patients with Gilbert's syndrome
exempted), either ALT or AST ≤ 1.5 ULN and ALP ≤ 1.5 ULN

Exclusion Criteria:

1. Locally advanced/inoperable breast cancer

2. Clinical evidence of metastatic disease

3. Diffuse or inflammatory tumours

4. Any history of invasive malignancy within 5 years of starting study treatment (other
than adequately treated basal cell carcinoma or squamous cell carcinoma of the skin
and cervical carcinoma in situ)

5. Evidence of bleeding diathesis and PTT and PT ≤ 1.5 x upper limit of normal

6. Concomitant use (defined as use within 4 weeks prior to entry) of HRT or any other
oestrogen-containing medication or supplement (including vaginal oestrogens and
phytoestrogens)

7. Previous use of oestrogen implants at ANY time.

8. Concomitant use of:

- Rifampicin and other CYP2C and 3A inducers such as rifabutin, rifapentine,
carbamazepine, phenobarbital, phenytoin and St. John's Wort

- Systemic carbonic anhydrase inhibitors

9. Any of the following cardiac criteria:

- Mean resting corrected QT interval (QTcf) > 450 ms obtained from 3
electrocardiograms (ECGs)

- Any clinically important abnormalities in rhythm, conduction or morphology of
resting ECG e.g. complete left bundle branch block, third degree heart block

- Any factors that increase the risk of QTc prolongation or risk of arrhythmic
events such as heart failure, hypokalaemia, congenital long QT syndrome, family
history of long QT syndrome or unexplained sudden death under 40 years of age or
any concomitant medication known to prolong the QT interval

10. Uncontrolled abnormalities of serum potassium, sodium, calcium or magnesium levels

11. Evidence of uncontrolled active infection

12. Evidence of significant medical condition or laboratory finding which, in the opinion
of the investigator, makes it undesirable for the patient to participate in the trial

13. Subjects unable to lie flat or fit into the scanner

14. Patients on occupational monitoring for radiation exposure

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Changes in FLT uptake as assessed by PET following 2 weeks of treatment with Irosustat

Outcome Time Frame:

Patients will have a baseline FLT-PET/CT scan and a follow-up scan after 2 weks of treatment with Irosustat

Safety Issue:

No

Principal Investigator

Carlo Palmieri, BSc MBBS PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Imperial Colllge London

Authority:

United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:

C/24/2011

NCT ID:

NCT01662726

Start Date:

August 2012

Completion Date:

August 2013

Related Keywords:

  • Breast Neoplasms
  • Breast Neoplasms
  • Neoplasms

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