Status and phase
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About
This study is looking at a new drug called AZD4547 which is being tested for the treatment of oestrogen receptor positive breast cancer. AZD4547 is a drug which specifically "blocks" proteins called fibroblast growth factor receptors (FGFR1) that are involved in the processes that help cancer cells to grow. These proteins may also be responsible for the development of resistance to hormonal therapies used to treat some breast cancers. AZD4547 is not yet approved for use in breast cancer and is therefore being used in this study as a research drug.
The investigators will also test the theory that it is not necessary for high levels of FGFR1 to be present in the body to see benefit from AZD4547. (Stage 1 only)
Full description
The study will be carried out in two stages. Stage 1 is to find a suitable dose of AZD4547 which can be used together with a class of drugs called nonsteroidal aromatase inhibitors (e.g. anastrozole or letrozole) i.e. a dose which does not cause too many unacceptable side effects.
Patients with hormone sensitive (oestrogen receptor positive) breast cancer, whose current treatment with anastrozole or letrozole has recently stopped working properly will be eligible for this stage.
Stage 2 will then assess the efficacy of AZD4547, based on the change in tumour size at 12 weeks (or progression if prior to week 12), when used in combination with either anastrozole or letrozole in patients with hormone sensitive (oestrogen receptor positive) breast cancer, who have progressed on treatment with either anastrozole or letrozole in any setting.
In both stages, the study will look at how well the new treatment is tolerated.
Each patient is only allowed to take part in either stage 1 or 2.
The study will be run in 9 Hospitals across England and Scotland.
Enrollment
Sex
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Volunteers
Inclusion and exclusion criteria
Inclusion Criteria Patients must fulfil all of the following criteria.
Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up
Aged ≥ 25 years of age (N.B. in line with other studies with AZD4574 and due to concerns of possible effects on the immature skeleton)
Post menopausal women. Women will be considered postmenopausal if they have had a bilateral oophorectomy or the following specific requirements apply:
Safety run-in:
Phase IIa:
Women under 50 years old would be considered post-menopausal if they have been amenorrhoeic for 24 months and have follicle-stimulating hormone (FSH) and oestradiol levels in the post-menopausal range.
Women aged 50 years and older would be considered post-menopausal if they have been amenorrhoeic for 12 months
Women rendered amenorrhoeic by adjuvant chemotherapy, who were premenopausal or perimenopausal prior to chemotherapy, must have been amenorrhoeic for at least 24 months
Perimenopausal women rendered amenorrhoeic from exposure to depot LHRH analogues*
Eastern Cooperative Oncology Group (ECOG) performance status 0-1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks
Histological confirmation of breast cancer with documented positive oestrogen receptor status (ER+) of primary or metastatic tumour tissue according to local laboratory parameters
Phase IIa: Mandatory provision of tumour biopsy for assessment of oncology biomarkers
Fulfils criteria for previous treatment of breast cancer*:
Safety run-in:
Phase IIa:
o Progressing or progression at some point during breast cancer treatment on endocrine therapy with a non-steroidal AI.*** Co-administration of a targeted agent with the non-steroidal AI is permitted providing all toxicities have recovered to CTCAE Grade 1 or below.
Prior chemotherapy in the advanced and adjuvant setting is permitted.
Prior treatment with exemestane with or without everolimus is permitted.
Safety run-in: At least one lesion (measurable and/or non-measurable) that can be accurately assessed by CT/MRI/plain x-ray at baseline and follow up visits Phase IIa: At least one lesion ≥ 10mm in the longest diameter at baseline (or ≥ 15mm in the short axis for nodal disease) that can be accurately measured with CT/MRI at baseline and is suitable for accurate repeated measurements. Patients with bone only metastatic cancer must have a lytic or mixed lytic-blastic lesion that can be accurately assessed by CT or MRI.
Safety run-in: Study entry must be preceded by a minimum of 21 days of anastrozole or letrozole treatment Phase IIa: No set duration of anastrozole or letrozole treatment prior to study entry.
Exclusion Criteria
Treatment with any of the following:
With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at time of starting study
Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids for at least 4 weeks prior to start of study treatment
Any evidence of severe or uncontrolled systemic diseases or active infection
Any of the following cardiac criteria:
Inadequate bone marrow reserve or organ function as defined by any one of the following parameters:
Haemoglobin < 9.0 g/dL (<90.0 g/L) Absolute neutrophil count (ANC) < 1.5 x 109 /L Platelet count < 100 x 109 /L Alanine aminotransferase > 2.5 x Upper Limit of Normal (ULN) if no demonstrable liver metastases or > 5 x ULN in the presence of liver metastases Aspartate aminotransferase > 2.5 x ULN if no demonstrable liver metastases or > 5 x ULN in the presence of liver metastases Total bilirubin > 1.5 x ULN if no demonstrable liver metastases or > 3 x ULN in the presence of liver metastases Creatinine > 1.5 times ULN or creatinine clearance <50ml/min Corrected calcium > ULN Phosphate > ULN
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 AZD4547 or anastrozole or letrozole
History of hypersensitivity to anastrozole or letrozole
History of another malignancy within 5 yrs prior to starting study treatment, except adequately treated basal or squamous cell carcinoma of the skin, carcinoma of the cervix and the disease under study
Any of the following ophthalmological criteria:*
Concurrent treatment with another investigational agent or use of another investigational agent within 30 days or 5 half lives, whichever is longer, preceding the first dose of study treatment
Concurrent treatment with prohibited medications and wash out period for that drug will not have been completed before starting study medication
Primary purpose
Allocation
Interventional model
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52 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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