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.
Overview
- Phase
- Phase 2
- Intervention
- Irosustat
- Conditions
- Locally Advanced Breast Cancer
- Sponsor
- Imperial College London
- Enrollment
- 27
- Locations
- 9
- Primary Endpoint
- Clinical benefit defined as complete response / partial response plus stable disease for at least 6 months (RECIST v1.1).
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief 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. 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •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
- •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.
Exclusion Criteria
- •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
- •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.
Arms & Interventions
Irosustat (Single arm study)
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.
Intervention: Irosustat
Outcomes
Primary Outcomes
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
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).(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).(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).(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.(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)(Patients will be followed up until disease progression, an expected average of 6 months)