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| ID | Type | Description | Link |
|---|---|---|---|
| 11-LO-1644 | Other Identifier | London Chelsea Research Ethics Committee |
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Patients with breast cancer, who are treated with curative intent, have a combination of surgery (excision of the tumor) and a course of medical therapy (chemotherapy or endocrine treatment). Both treatments are associated with significant side effects. Chemotherapy is associated with nausea, vomiting, hair loss and bone marrow suppression, whereas endocrine therapy is associated with arthritis and menopausal symptoms. Patients taking either chemotherapy or endocrine treatment may experience a range of side effects. The range and severity of side effects experienced vary from patient to patient. Little or nothing is known about the reason for this difference.
The aim of the investigators proposal is to develop a pretreatment test to identify patients who are likely to undergo moderate to severe side effects, and therefore help doctors and patients plan and optimize medical therapy. The pretreatment test will be based on identifying a metabolic profile which can differentiate those patients who are likely to have severe or moderate side effects from those with either no or mild side effects. To do this, the investigators will take urine and blood samples from patients before and after the administration of endocrine treatment or chemotherapy and generate metabolic profiles.
Furthermore, the investigators aim to gain an understanding into why side effects experienced between different patients are so variable. To do this the investigators plan to perform cytokine analysis, targeted genetic analysis and pharmaokinetic analysis on blood sample collected from patients before and after treatment has commenced. Patients who have planned surgical excision of tumor and are recommended to receive medical therapy before or after surgery would be invited to join the study. Each patient will be required to make additional visits to the hospital to complete questionnaires regarding side effects experienced and for sample (urine and blood) collection. The investigators plan to recruit 168 patients.
Patients with breast cancer are treated with a combination of surgery and medical treatment (either before (neoadjuvant) or after (adjuvant) surgery). Eligible patients will be identified by the oncologist and from the multidisciplinary meeting.
Once eligible patients have been identified they will be informed of the study by their oncologist, and then approached by the research team who will give them a patient information leaflet, discuss the study, answer any questions and ask the patient to sign a consent form if they are would like to participate in the study. The consent form must be signed before any study related procedures are performed.
Patients who have had surgery prior to receiving medical treatment (i.e. patients planned to receive adjuvant treatment, or patients who have a sentinel lymph node biopsy prior to starting neoadjuvant treatment) will have blood and urine samples taken before they have their surgery, at the preassessment surgical appointment.
The week before the patient starts medical therapy (either chemotherapy or endocrine treatment) the patient will need to attend Charing Cross Hospital for the following procedures (this may be an extra visit, depending on hospital appointments):
The patient will be asked to return to Charing Cross Hospital 24 hours later after an overnight fast for (this will be an extra visit): • Fasted blood and urine samples for metabolic profiling.
It is important to get fasted samples from patients, as diet influences the metabolic profile. Therefore to try to eliminate diet as a confounder it is important to get a fasted sample. Additionally, at the time of collection of blood and urine samples for metabolic profile analysis patients will be asked when they last ate, what they last ate and any specific dietary preferences/requirements (i.e. vegetarian, gluten free diet).
Further tests differ depending on whether the patient is receiving chemotherapy or endocrine treatment.
Patients receiving chemotherapy have 6 cycles, each cycle last 21 days. There are two types of chemotherapy given for breast cancer which are FEC (6 cycles of 5fluorouracil, epirubicin and cyclophosphamide) or FECD (3 cycles of 5fluorouracil, epirubicin and cyclophosphamide followed by 3 cycles of docetaxel). Patients receiving all types of chemotherapy (FEC and FECD) patients will be required to attend at the following time for procedures are explained below:
Cycle 1, day 2
o 24 hours after the patient received their chemotherapy treatment we will take urine and blood samples for metabolic profiling, and blood samples for routine blood tests (haematology and biochemistry) and cytokine analysis.
Cycle 2, day 1
Cycle 2, day 1 (optional assessment)
o Three blood samples will be taken during the following 4 hours for pharmacokinetic analysis of cylophosphamide and epirubicin. If possible all samples will be taken from the cannula through which the chemotherapy was administered.
Cycle 2, day 2 (optional assessment) o A blood sample will be taken 24 hours after the chemotherapy was given for pharmacokinetic analysis of cyclophosphamide.
Cycle 2, day 3 (optional assessment)
o A blood sample will be taken 48 hours after the chemotherapy was given for pharmacokinetic analysis of epirubicin.
Cycle 6, day 21
If patients are on FECD chemotherapy, they will attend at the above time points, but they will additionally be asked to attend after their docetaxel has commenced. This is required to test whether docetaxel has a different reaction in the body to the previous chemotherapy given. Patients will be asked to attend at the following time points for the following procedures:
Cycle 4, day 2
o 24 hours after the patient received their chemotherapy treatment we will take urine and blood samples for metabolic profiling, and blood samples for routine blood tests (haematology and biochemistry) and cytokine analysis.
o Two questionnaires (questionnaire based on adverse effects experienced and QOL questionnaire) will be completed with research staff
o This will be an extra visit
Cycle 5, day 1
If patients have consented for optional pharmacokinetic analysis the following sample will also be taken.
• Cycle 5, day 1
o A blood sample will be taken at the end of the chemotherapy infusion and 6 hours after the infusion completed. If possible the blood samples will be taken from the cannula (the first 10mls taken from the cannula will need to be discarded to avoid contamination).
Patients receiving endocrine treatment will be asked to attend at the following time points after starting treatment for procedures listed below, in addition to baseline assessments described above:
Day 2
Day 21
At 5 months
All procedures and interviews will be conducted at Charing Cross Hospital. All patients will be enrolled in the study for 5 months. However, for patients receiving chemotherapy, if there has been a change in treatment schedule by the oncologist the time the patient will spend in the study will be increased in accordance with changes made to treatment schedule (i.e. if cycle 4 (docetaxel) is started 1 week late, then the time in the study will be 5 months and 1 week).
For patients receiving neoadjuvant treatment (chemotherapy or endocrine treatment before surgery) we will look at imaging and pathology reports to establish how the tumour has responded to treatment.
We aim to recruit 168 patients, 84 receiving endocrine therapy (either an oestrogen receptor antagonist or aromatase inhibitor) and 84 receiving cytotoxic chemotherapy (FEC or FECD).
The study will be conducted in 5 phases:
The results will be analysed and published (in both presentations and a peer reviewed journal) at the end of the study. No patient identifiable information will be present in these publications. As all tests are carried out for research purposes and will be of no direct benefit to patients participating in this study, there are no plans to inform patients of their individual results. Patients will be informed of the overall results from the study that may result in a publication.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients receiving endocrine treatment for breast cancer | Patients who are treated with tamoxifen, anastrozole or letrozole before or after surgery for breast cancer. | ||
| Patients receiving chemotherapy for breast cancer | Patients receiving FEC (5-FU, cyclophosphamide, epiribicin) or FEC-D (FEC for 3 cycles, followed by 3 cycles of docetaxel). |
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| Measure | Description | Time Frame |
|---|---|---|
| The primary outcome measure for the study is to determine the relationship between metabonomics spectrum and side effects from chemotherapy and endocrine therapy for patients receiving treatment for breast cancer. | To identify a pre-treatment metabolic profile to predict patients who will experience moderate to severe side effects. | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Conduct pharmokinetic analysis of drugs administered and determine relationship between pharmacokinetics and severity of side effects experienced. | Measure pharmokinetics of each drug to try and ascertain underlying reasons for differences in toxicity. | 2 years |
| Conduct cytokine analysis pre and post treatment, to determine relationship with severity of side effects experienced. |
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Inclusion Criteria:
Exclusion Criteria:
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Patients who have newly diagnosed primary breast cancer who will be receiving chemotherapy (FEC and FEC-D regimes only) or endocrine treatment (anastrozole, letrozole or tamoxifen only).
All new patients with Breast Cancer are discussed at the multidisciplinary team meeting (MDT) where they will be identified for the study. Patients will be identified by the oncologist and the multidisciplinary team (i.e the existing clinical care team).
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| Name | Affiliation | Role |
|---|---|---|
| Charles Coombes | Imperial College London | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Charing Cross Hospital | London | W6 8RF | United Kingdom |
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plasma/serum urine buffy coat - for purposes of DNA extraction
| 2 years |
| Conduct targeted genetic analysis to determine relationship with severity of side effects experienced. | To identify known SNPs implicated in toxicity to metabolic profile/biomarkers found. | 2 years |
| To find underlying mechanism to explain the interpatient variability in severity of side effects experienced using above techniques (i.e. metabolic profile, pharmacokinetic analysis, cytokine analysis and targeted genetic analysis). | 2 years |
| To identify a biomarker based on metabnomic profiling for response to treatment for those receiving neoadjuvant treatment. | 2 years |