Predictive Model of Therapy Outcomes in Breast Cancer Patients
|First Received Date ICMJE||January 25, 2012|
|Last Updated Date||March 25, 2015|
|Start Date ICMJE||February 2012|
|Primary Completion Date||August 2014 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||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. [ Time Frame: 2 years ]
To identify a pre-treatment metabolic profile to predict patients who will experience moderate to severe side effects.
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01563211 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Predictive Model of Therapy Outcomes in Breast Cancer Patients|
|Official Title ICMJE||Predictive Modelling of Short Term Outcomes Following Systemic Neo-adjuvant and Adjuvant Therapy in Breast Cancer Patients|
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:
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:
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:
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.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Observational Model: Cohort
Time Perspective: Prospective
|Target Follow-Up Duration||Not Provided|
|Biospecimen||Retention: Samples With DNA
plasma/serum urine buffy coat - for purposes of DNA extraction
|Sampling Method||Non-Probability Sample|
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).
|Condition ICMJE||Toxicity From Medication (Endocrine Treatment and Chemotherapy) Given for Breast Cancer Treatment.|
|Intervention ICMJE||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||August 2014|
|Primary Completion Date||August 2014 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United Kingdom|
|Removed Location Countries|
|NCT Number ICMJE||NCT01563211|
|Other Study ID Numbers ICMJE||72393/271478/14/611
11-LO-1644 ( Other Identifier: London Chelsea Research Ethics Committee )
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Imperial College London|
|Study Sponsor ICMJE||Imperial College London|
|Collaborators ICMJE||Not Provided|
|PRS Account||Imperial College London|
|Verification Date||March 2012|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP