A Cancer Research UK randomised phase II trial of ATN-224 (copper binding agent) in combination with exemestane versus exemestane alone in post-menopausal women with recurrent or advanced, oestrogen and/or progesterone receptor positive breast cancer
- Conditions
- recurrent or advanced oestrogen and/or progesterone receptor positive breast cancerMedDRA version: 9.1 Level: LLT Classification code 10006198 Term: Breast cancer recurrent
- Registration Number
- EUCTR2007-005752-16-GB
- Lead Sponsor
- Cancer Research UK
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 111
1. Histologically proven oestrogen and/or progesterone receptor positive breast cancer as defined by at least one of the criteria below:-
Oestrogen Receptor Positivity
• a score of 3 or more on a scale (range of 0 to 8), or equivalent score from other grading methods; representing the intensity and percentage of positive-staining tumour cells by immunohistochemistry.
• = 5 fmol/mg protein by ligand binding assay or ELISA.
Progesterone Receptor Positivity
• a score of 3 or more on a scale (range of 0 to 8) ), or equivalent score from other grading methods; representing the intensity and percentage of positive-staining tumour cells by immunohistochemistry.
2. Patients with recurrent or advanced disease who have received an anti-oestrogen and/or non steroidal aromatase inhibitor as adjuvant treatment or patients who have received an anti-oestrogen or a non-steroidal aromatase inhibitor as first line treatment for advanced disease.
3. Post-menopausal women as defined by one of the following:
• surgical or radiation-induced, bilateral oophorectomy at least 1 year in the past;
• in women with an intact uterus, no menstrual periods for 12 consecutive months with no other biological or physiological cause;
• age 55 years or older;
4. Measurable/evaluable disease as measured by clinical examination, X-ray, computerised tomography (CT) or MRI scan, with at least one lesion that can be followed for response.
5. Life expectancy of at least 6 months.
6. Prior therapy allowed:
Adjuvant or neoadjuvant treatment with tamoxifen
Adjuvant or neoadjuvant treatment with a non-steroidal aromatase inhibitor
Adjuvant/neoadjuvant chemotherapy
Tamoxifen or non-steroidal aromatase inhibitor as first line treatment in the metastatic setting
7. Patients with bone metastases only are eligible provided they have at least one lytic lesion (not previously irradiated or planned for irradiation) that can be followed by X-ray or CT scanning. Independent review of X-ray/CT scans will be performed.
8. Patients with cutaneous skin metastases only are eligible provided the skin lesions are > 10 mm and can be followed by good quality photography (ideally performed by medical photography) with a ruler included in the photograph.
9. World Health Organisation (WHO) performance status of 0 to 2
10. 18 years or over.
11. Written (signed and dated) informed consent, and be capable of co-operating with treatment and follow-up.
12. Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week before the patient starts study treatment.
Lab Test Value required
Haemoglobin (Hb) =9.0 g/dl
Neutrophils =1.5 x 10(9)/L
Platelets =100 x 10(9)/L
Serum bilirubin =1.5 x upper limit of normal (ULN)
Alanine amino-transferase (ALT) and/or aspartate amino-transferase (AST)
= 2.5 x ULN, unless raised due to tumour in which case up to 5 x ULN is
1. Radiotherapy (except to control pain or prevent fracture or in the adjuvant setting). Chemotherapy except in the adjuvant setting.
2. Tumours with HER2 over-expression [3+ score as assessed by immunohistochemistry] or HER2 gene amplification [positive result by fluorescence in situ hybridisation (FISH)].
3. Prior treatment with exemestane.
4. Currently receiving treatment with a luteinizing hormone-releasing hormone (LH-RH) analogue.
5. Currently receiving treatment with oral bisphosphonates (i.v. bisphosphonates are permitted).
6. Currently receiving chronic steroid therapy for concurrent illness or cancer. [Short-term steroid use for concurrent illness is allowed, eg for acute asthma].
7. History of malabsorption syndromes or other gastrointestinal disorders that may affect ATN-224 absorption, including bowel obstruction, celiac disease, sprue, cystic fibrosis
8. History of allergic reactions attributed to compounds of similar chemical or biologic composition to ATN-224, omeprazole (or other proton pump inhibitor), or exemestane.
9. Receiving any other copper-binding drug during the study (eg penicillamine or trientine).
10. Use of copper- or zinc-containing vitamins or supplements during the study.
11. Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities that in the opinion of the Investigator and the Drug Development Office (DDO) should not exclude the patient.
12. Clinically apparent brain metastases.
13. Major thoracic and/or abdominal surgery in the preceding four weeks from which the patient has not recovered.
14. At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
15. Known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV).
16. Current malignancies of other types, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. [Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for 5 years and are deemed at low risk for recurrence, are eligible for the study].
17. Concurrent congestive heart failure or prior history of class III/IV cardiac disease (New York Heart Association [NYHA]).
18. Any other condition which in the Investigator’s opinion would not make the patient a good candidate for the clinical trial.
19. Is a participant or plans to join in another interventional clinical study, whilst taking part in this Phase II study of ATN-224. Participation in an observational study would be acceptable.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method