Locally Advanced Breast CancerPhase 2IRISNCT01785992
A Study of the Safety and Effectiveness of Irosustat When Added to an AI in ER+ve Locally Advanced or Metastatic Breast Cancer.
A Phase 2 study testing Irosustat in people with Locally Advanced Breast Cancer and Metastatic Breast Cancer, run by Imperial College London at 9 sites in United Kingdom.
Trial summary
70% of breast cancers that occur in postmenopausal women rely on the hormone oestrogen to grow and are likely to respond to hormone treatment. This type of treatment reduces the amount of oestrogen in the body, slowing the growth of cancer or stopping it altogether. Read more about this study
- Who is it for?
- Ages 25 years and older, women only
- Conditions the study is for
- Locally Advanced Breast Cancer, Metastatic Breast Cancer
- What is being tested?
- Irosustat
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 9 sitesUnited Kingdom
- Study dates
- Oct 2012to Dec 2014
- Phase
- Phase 2
- 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 25 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent prior to admission to this study.
- Aged ≥ 25 years of age.
- Histologically confirmed ER+ve primary or metastatic breast cancer.
- Locally advanced or metastatic breast cancer treated with 1st line AI treatment with either a documented objective response (CR/PR) or disease stabilisation (SD) for at least 6 months prior to disease progression.
- Postmenopausal as defined by any of the following criteria:
- Amenorrhoea for at least 6 months prior to study entry and estradiol and LH/FSH in the postmenopausal range on local laboratory analysis whilst taking a 3rd generation AI during the screening phase of the study.
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- Amenorrhoea during combination treatment with ovarian suppression (e.g. goserelin) and an AI in which case estradiol should be below the limit of detection of the standard local laboratory assay during the screening phase of the study.
- ECOG performance status 0 to 2.
- Measurable and/or evaluable sites of locally advanced or metastatic disease that can be accurately assessed by CT/MRI scan at baseline and follow up visits (RECIST v1.1).
- N.B Patients with bone metastasis are eligible provided they have evaluable metastases sites that can be followed (X-Ray or MRI/CT scanning). Patients on established bisphosphonate treatment for at least 3 months are eligible for entry into the trial and are allowed to continue with bisphosphonate treatment.
- Adequate organ function as defined by (Haemoglobin (Hb) ≥ 9 g/dL; Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L; Platelet count (Plts) ≥ 100 ≥ 109/L; White Blood Cell (WBC) ≥ 3.0 x 109/L; Serum albumin ≤ 1.5 upper limit of normal (ULN); Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 3 x ULN if no demonstrable liver metastases or ≤ 5 x ULN in the presence of liver metastases; alkaline phosphatase (ALP) ≤ 5 x ULN; Total bilirubin ≤ 1.5 x ULN if no demonstrable liver metastases or ≤ 3 x ULN in the presence of liver metastases; Creatinine ≤ 1.5 x ULN or creatinine clearance >50ml/min).
- Life expectancy of ≥3 months.
Who cannot join
- Human epidermal growth factor Receptor-2 (HER2) positive cancer.
- Discontinuation of current AI therapy for > 21 days prior to study entry.
- N.B If the patient has discontinued the AI within this period they can be restarted on the same AI. This must be continued for at least 7 days before introducing the IMP. Baseline investigations must be performed in timeframes related to the start of the IMP, not the AI.
- Rapidly progressive, life-threatening metastases, including any of the following:
- Patients with active parenchymal brain or leptomeningeal involvement
- Symptomatic lymphangitis carcinomatosis
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- Extensive visceral metastases requiring chemotherapy.
- Patients with a history of another primary malignancy within 5 years prior to starting study treatment, except adequately treated basal or squamous cell carcinoma of the skin, carcinoma in site and the disease under study.
- More than one prior line of chemotherapy for locally advanced or metastatic disease.
- AI therapy given in combination with another endocrine agent with the exception of a GnRH agonist.
- Radiotherapy to measurable lesion within 2 months of treatment start.
- Systemic corticosteroids for ≥ 15 days within the last 4 weeks.
- 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.
- Concurrent therapy with any other investigational agent.
- Concomitant use within 14 days prior to commencement of study treatment 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 as calculated by Fridericia's formula 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 (corrected) phosphate or magnesium levels.
- Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated investigational medicinal product (IMP) or previous significant bowel resection that would preclude absorption of Irosustat or the AI.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United Kingdom9 sites
Mid Essex Hospital Services NHS Trust
Chelmsford, CM1 7ET
NHS Lothian
Edinburgh, EH1 3EG
NHS Greater Glasgow and Clyde
Glasgow, G12 0YN
Royal Liverpool and Broadgreen University Hospital
Liverpool, L7 8XP
Royal Free London
London, NW3 2QG
West Middlesex University Hospital NHS Trust
London, TW7 6AF
Imperial College Healthcare NHS Trust
London, W6 8RF
University College London Hospitals NHS Foundation Trust
London, WC1E 6BT
The Christie NHS Foundations Trust
Manchester, M204BX
About this study
Official title: A Phase II Study to Assess the Safety and Efficacy of the Steroid Sulfa-tase Inhibitor Irosustat When Added to an Aromatase Inhibitor in ER Positive Locally Advanced or Metastatic Breast Cancer Patients.
70% of breast cancers that occur in postmenopausal women rely on the hormone oestrogen to grow and are likely to respond to hormone treatment. This type of treatment reduces the amount of oestrogen in the body, slowing the growth of cancer or stopping it altogether. One type of hormone treatment, aromatase inhibitors (AIs), works by stopping the body from making oestrogen. Currently, women with locally advanced or metastatic breast cancer that is not being controlled by one class of AI are switched to the other class of AI. The reason for this is that some cancer cells can become resistant to one class but are still sensitive to the other class. However, oestrogen can be made in the body by two pathways and AIs block only one of these pathways. A new drug called Irosustat can reduce the production of oestrogen in the body by blocking the second pathway. This study is investigating whether adding Irosustat to AI treatment i.e. blocking both pathways at the same time, can further reduce the amount of oestrogen in the body and therefore control the breast cancer better.
27 postmenopausal women with oestrogen receptor positive locally advanced or metastatic breast cancer that is not being controlled by their current AI treatment will be recruited in this study from 9 United Kingdom (UK) hospitals. Eligible patients will receive 40mg of Irosustat once daily in addition to the AI on which they progressed. Patients will receive Irosustat for as long as it controls their cancer or until they have side effects that stop them from taking treatment. Patients will be seen monthly for the first 6 months and every 3 months thereafter. Participating patients will also be given the option to take part in the exploratory part of this study by donating tissue and blood samples.
- Being tested
- Irosustat
- Keywords
- Oestrogen receptor, Locally advanced, Metastatic, Breast cancer, Sulfatase inhibitor
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IrosustatDrug
Also called STX64, 667 Coumate, BN83495
Patients will receive 40mg of Irosustat once daily in addition to the aromatase inhibitor on which they progressed until disease progression or development of unacceptable toxicities.
| Study group | Role | What they receive |
|---|---|---|
| Irosustat (Single arm study) | Other | Patients will receive 40mg of Irosustat once daily in addition to the aromatase inhibitor on which they progressed until disease progression or the development of unacceptable toxicities. Receives: Drug: Irosustat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical benefit defined as complete response / partial response plus stable disease for at least 6 months (RECIST v1.1).
Measured: Patients will be followed up until disease progression, an expected average of 6 months
Secondary outcomes (5)
Duration of clinical benefit as defined by the number of days from start of study drug to the first evidence of disease progression or death due to any cause (RECIST v1.1).
Measured: Patients will be followed up until disease progression, an expected average of 6 months
Progression Free Survival defined as time from randomisation to first evidence of disease progression or death due to any cause (RECIST v1.1).
Measured: Patients will be followed up until disease progression, an expected average of 6 months
Safety and tolerability as assessed by the collection of adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE v 4.03).
Measured: Patients will be followed up until disease progression, an expected average of 6 months
To measure alterations in circulating steroid hormones and correlation of these measures with clinical outcome.
Measured: 0,1,2,3,4,5,6,9,12 months after study entry
Objective response rate as defined by complete response and partial response (RECIST v1.1)
Measured: Patients will be followed up until disease progression, an expected average of 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2013 (estimated)
- Study startOct 2012
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Breast CancerStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer Research UK
- Responsible party
- Sponsor
- Investigators
- Carlo Palmieri, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01785992
- Sponsor's protocol ID
- C/22/2011
- Other IDs
- 2011-005680-25
- Acronym
- IRIS
- Status last verified
- Mar 2014
- First submitted
- 4 Feb 2013
- Last updated
- 24 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study to Assess the Safety and Efficacy of the Steroid Sulfa-tase Inhibitor Irosustat When Added to an Aromatase Inhibitor in ER Positive Locally Advanced or Metastatic Breast Cancer Patients.
- ClinicalTrials.gov ID
- NCT01785992
- Acronym / sponsor ID
- IRIS / C/22/2011
- Keywords
- Oestrogen receptor, Locally advanced, Metastatic, Breast cancer, Sulfatase inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Cancer Research UK
- Study start
- Oct 2012
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 7 Feb 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.
70% of breast cancers that occur in postmenopausal women rely on the hormone oestrogen to grow and are likely to respond to hormone treatment. This type of treatment reduces the amount of oestrogen in the body, slowing the growth of cancer or stopping it altogether. One type of hormone treatment, aromatase inhibitors (AIs), works by stopping the body from making oestrogen. Currently, women with locally advanced or metastatic breast cancer that is not being controlled by one class of AI are switched to the other class of AI. The reason for this is that some cancer cells can become resistant to one class but are still sensitive to the other class. However, oestrogen can be made in the body by two pathways and AIs block only one of these pathways. A new drug called Irosustat can reduce the production of oestrogen in the body by blocking the second pathway. This study is investigating whether adding Irosustat to AI treatment i.e. blocking both pathways at the same time, can further reduce the amount of oestrogen in the body and therefore control the breast cancer better.
27 postmenopausal women with oestrogen receptor positive locally advanced or metastatic breast cancer that is not being controlled by their current AI treatment will be recruited in this study from 9 United Kingdom (UK) hospitals. Eligible patients will receive 40mg of Irosustat once daily in addition to the AI on which they progressed. Patients will receive Irosustat for as long as it controls their cancer or until they have side effects that stop them from taking treatment. Patients will be seen monthly for the first 6 months and every 3 months thereafter. Participating patients will also be given the option to take part in the exploratory part of this study by donating tissue and blood samples.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Irosustat (Single arm study) | Other | Drug: IrosustatPatients will receive 40mg of Irosustat once daily in addition to the aromatase inhibitor on which they progressed until disease progression or the development of unacceptable toxicities. |
Who may qualify
- Ages
- 25 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Written informed consent prior to admission to this study.
- Aged ≥ 25 years of age.
- Histologically confirmed ER+ve primary or metastatic breast cancer.
- Locally advanced or metastatic breast cancer treated with 1st line AI treatment with either a documented objective response (CR/PR) or disease stabilisation (SD) for at least 6 months prior to disease progression.
- Postmenopausal as defined by any of the following criteria:
Key exclusion criteria (24 listed)
- Human epidermal growth factor Receptor-2 (HER2) positive cancer.
- Discontinuation of current AI therapy for > 21 days prior to study entry.
- N.B If the patient has discontinued the AI within this period they can be restarted on the same AI. This must be continued for at least 7 days before introducing the IMP. Baseline investigations must be performed in timeframes related to the start of the IMP, not the AI.
- Rapidly progressive, life-threatening metastases, including any of the following:
- Patients with a history of another primary malignancy within 5 years prior to starting study treatment, except adequately treated basal or squamous cell carcinoma of the skin, carcinoma in site and the disease under study.
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 |
|---|---|---|
| IrosustatAlso: STX64, 667 Coumate, BN83495Patients will receive 40mg of Irosustat once daily in addition to the aromatase inhibitor on which they progressed until disease progression or development of unacceptable toxicities. | Drug | Irosustat (Single arm study) |
Primary outcome
Clinical benefit defined as complete response / partial response plus stable disease for at least 6 months (RECIST v1.1).
Time frame: Patients will be followed up until disease progression, an expected average of 6 months
5 secondary outcomes
Duration of clinical benefit as defined by the number of days from start of study drug to the first evidence of disease progression or death due to any cause (RECIST v1.1).
Time frame: Patients will be followed up until disease progression, an expected average of 6 months
Progression Free Survival defined as time from randomisation to first evidence of disease progression or death due to any cause (RECIST v1.1).
Time frame: Patients will be followed up until disease progression, an expected average of 6 months
Safety and tolerability as assessed by the collection of adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE v 4.03).
Time frame: Patients will be followed up until disease progression, an expected average of 6 months
To measure alterations in circulating steroid hormones and correlation of these measures with clinical outcome.
Time frame: 0,1,2,3,4,5,6,9,12 months after study entry
Objective response rate as defined by complete response and partial response (RECIST v1.1)
Time frame: Patients will be followed up until disease progression, an expected average of 6 months
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 24 Mar 2015.
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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.
Carlo Palmieri principal investigator
Imperial College London
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Irosustat in people with Locally Advanced Breast Cancer and Metastatic Breast Cancer, run by Imperial College London at 9 sites in United Kingdom.
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 12 inclusion and 24 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 24 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Clinical benefit defined as complete response / partial response plus stable disease for at least 6 months (RECIST v1.1). (time frame: Patients will be followed up until disease progression, an expected average of 6 months). 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 24 Mar 2015.