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A Study to Assess the Ability of a Novel Endocrine Treatment for Breast Cancer, Irosustat, to Slow Down Cancer Growth (IPET)

Primary Purpose

Breast Neoplasms

Status

Terminated

Phase

Phase 2

Locations

United Kingdom

Study Type

Interventional

Intervention

Irosustat

About this trial

This is an interventional treatment trial for Breast Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Written informed consent to participate in the trial
18 years of age or older
Histologically confirmed ER +ve breast cancer (Allred ≥ 3)
Any HER2 status
Tumour measuring ≥ 15mm in longest diameter on ultrasound (US) examination
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
Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
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:

Locally advanced/inoperable breast cancer
Clinical evidence of metastatic disease
Diffuse or inflammatory tumours
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)
Evidence of bleeding diathesis and PTT and PT ≤ 1.5 x upper limit of normal
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)
Previous use of oestrogen implants at ANY time.
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
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
Uncontrolled abnormalities of serum potassium, sodium, calcium or magnesium levels
Evidence of uncontrolled active infection
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
Subjects unable to lie flat or fit into the scanner
Patients on occupational monitoring for radiation exposure

Sites / Locations

Imperial College Healthcare NHS Trust

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Irosustat

Arm Description

Irosustat 40mg OD for a minimum of 2 weeks until follow up FLT-PET/CT. For those patients consented to a repeat tumour biopsy, treatment will be extended to that day before the procedure.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

To characterize the pharmacodynamic profile of Irosustat by measuring peripheral blood steroid hormone levels

To evaluate safety and tolerability of Irosustat by collecting toxicities according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 4.03: June 14, 2010)

Full Information

NCT ID

NCT01662726

First Posted

August 7, 2012

Last Updated

March 11, 2016

Sponsor

Imperial College London

Collaborators

National Institute for Health Research, United Kingdom, Ipsen, Imperial College Healthcare NHS Trust, Guy's and St Thomas' NHS Foundation Trust, University of Southern California, QPS Netherlands B.V.

1. Study Identification

Unique Protocol Identification Number

NCT01662726

Brief Title

A Study to Assess the Ability of a Novel Endocrine Treatment for Breast Cancer, Irosustat, to Slow Down Cancer Growth

Acronym

IPET

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2013

Overall Recruitment Status

Terminated

Why Stopped

Recruitment challenging: lack of suitable pts; recruiting so soon after diagnosis; competing studies. Funding ended despite extensions to grant.

Study Start Date

August 2012 (undefined)

Primary Completion Date

July 2014 (Actual)

Study Completion Date

December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Imperial College London

Collaborators

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This study is investigating the effects of a new hormone treatment for breast cancer called Irosustat. Seventy percent of breast cancers in post-menopausal wome rely on oestrogen to grow therefore are likely to respond to hormone therapy. Irosustat blocks a different pathway of steroid synthesis to Aromatase, reducing in this way oestrogen levels in the body. As less oestrogen reaches the breast cancer, it grows more slowly or stops growing altogether. IPET will recruit postmenopausal women with early, hormone sensitive, treatment naive breast cancer will receive 40mg of Irosustat once daily for 2 weeks. The effects of Irosustat on breast cancer will be evaluated by PET scans (Positron Emission Tomography) using a radioactive substance called FLT as a tracer. The scans will be performed in a PET-CT scanner which combines a PET scan and a CT scan (Computer Tomography) into one scan. This type of scan can show how body tissues are working, as well as what they look like. FLT-PET scans will be performed before and following treatment with Irosustat. As cancer cells grow faster than the normal cells around them, they will take up more of the radioactive substance, and so stand out clearly on the scan. If Irosustat is slowing down the cancer growth, the cancer will take up less of the tracer. Blood samples will be taken at regular intervals to assess what the new drug does to the body and the safety and tolerability of Irosustat will be assessed. The study incorporates translation aspects/endpoints which are based on the collection of tumour biopsies before and after treatment with Irosustat although the later biopsy is not mandatory.

Detailed Description

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: Pharmacodynamic profile of Irosustat Safety and tolerability of Irosustat Study Population: Postmenopausal women with early, treatment naïve, ER +ve breast cancer

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Neoplasms

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

13 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Irosustat

Arm Type

Experimental

Arm Description

Irosustat 40mg OD for a minimum of 2 weeks until follow up FLT-PET/CT. For those patients consented to a repeat tumour biopsy, treatment will be extended to that day before the procedure.

Intervention Type

Drug

Intervention Name(s)

Irosustat

Other Intervention Name(s)

BN83495, STX64, 667-coumate

Intervention Description

Irosustat will be administered once daily in 40mg tablets. Treatment will start the day after the baseline FLT-PET and will be continued for a minimum of 2 weeks until the follow up FLT PET scan. For those patients who have consented to a repeat tumour biopsy, treatment will be extended to the day before the procedure. Study medication should be taken in the morning under fasting conditions with a glass of water, 30 minutes before breakfast.

Primary Outcome Measure Information:

Title

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

Time Frame

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

Secondary Outcome Measure Information:

Title

To characterize the pharmacodynamic profile of Irosustat by measuring peripheral blood steroid hormone levels

Time Frame

Blood samples will be drawn from patients on day 1, day 7, day 14 and 28 days post administration of the last dose of Irosustat

Title

To evaluate safety and tolerability of Irosustat by collecting toxicities according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 4.03: June 14, 2010)

Time Frame

Patients will be assesed at baseline, day 7, day 14 and at 30 days following the last dose of Irosustat. Patients who have consented to an optional post treatment tumour biopsy will attend an extra study visit.

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Written informed consent to participate in the trial 18 years of age or older Histologically confirmed ER +ve breast cancer (Allred ≥ 3) Any HER2 status Tumour measuring ≥ 15mm in longest diameter on ultrasound (US) examination 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 Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 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: Locally advanced/inoperable breast cancer Clinical evidence of metastatic disease Diffuse or inflammatory tumours 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) Evidence of bleeding diathesis and PTT and PT ≤ 1.5 x upper limit of normal 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) Previous use of oestrogen implants at ANY time. 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 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 Uncontrolled abnormalities of serum potassium, sodium, calcium or magnesium levels Evidence of uncontrolled active infection 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 Subjects unable to lie flat or fit into the scanner Patients on occupational monitoring for radiation exposure

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Carlo Palmieri, BSc MBBS PhD

Organizational Affiliation

Imperial Colllge London

Official's Role

Principal Investigator

Facility Information:

Facility Name

Imperial College Healthcare NHS Trust

City

London

ZIP/Postal Code

W6 8RF

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

A Study to Assess the Ability of a Novel Endocrine Treatment for Breast Cancer, Irosustat, to Slow Down Cancer Growth

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