Chemotherapy on Methylation Patterns in Breast Tumor Tissue Correlating With Clinical Response and Outcomes
|ClinicalTrials.gov Identifier: NCT00698477|
Recruitment Status : Unknown
Verified June 2008 by National University Hospital, Singapore.
Recruitment status was: Recruiting
First Posted : June 17, 2008
Last Update Posted : June 17, 2008
|First Submitted Date||June 15, 2008|
|First Posted Date||June 17, 2008|
|Last Update Posted Date||June 17, 2008|
|Start Date||October 2007|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures||Not Provided|
|Original Primary Outcome Measures||Not Provided|
|Change History||No Changes Posted|
|Current Secondary Outcome Measures||Not Provided|
|Original Secondary Outcome Measures||Not Provided|
|Current Other Outcome Measures||Not Provided|
|Original Other Outcome Measures||Not Provided|
|Brief Title||Chemotherapy on Methylation Patterns in Breast Tumor Tissue Correlating With Clinical Response and Outcomes|
|Official Title||Study of the Effect of Chemotherapy on Methylation Patterns in Breast Tumor Tissue and Paired Plasma Samples and Correlation With Clinical Response and Outcomes|
Rationale: The optimal timing of sampling for methylation analysis that is reflective of the tumors response to chemotherapy is not known. How soon methylation changes are observed, whether they are high within 24 hours, as that tumor responds to chemotherapy, or whether changes can be observed only some time after one cycle of chemotherapy will be studied. (3) To also identify methylation pattern changes in breast tumor tissue after one cycle of chemotherapy.
Rationale: To look for a correlation with plasma methylation patterns
(1) To correlate our observed patterns of methylation pre- and post-treatment with clinical parameters such as clinical and/or radiological response and patient outcome.
In advanced breast cancer, it is often difficult to predict which patients will respond favorably to systemic therapy to decide on treatment duration or options while minimizing exposure to toxic effects. Our goal is to examine using locally advanced and metastatic breast cancer tumor tissue and plasma, the methylation profile patterns pre- and post chemotherapy of a panel of biomarkers most commonly expressed in breast cancer and correlate them with tumor response and patient outcome.
Our hypothesis is that DNA methylation pattern changes at baseline and early into a course of systemic therapy can predict disease response or progression as well as survival. In the long term, this could prove clinically useful in limiting exposure to ineffective regimens and allowing earlier identification of more effective systemic therapy.
Core biopsies of breast tumor tissue are taken at baseline and after cycle 1 of docetaxel/ketoconazole. Plasma samples are drawn at baseline, 24 hours after cycle 1 chemotherapy and 24 hours before cycle 2. Thirty patients' specimens (60 core biopsies and 90 plasma samples) will be utilized. Quantitative multiplex methylation-specific PCR will be used for analyses of several tumor suppressor genes including APC1, Cyclin D2, RARB, RASSF1A, Twist, Hin1 and GSTP1. From this data, we will identify a preliminary gene panel associated with breast cancer which undergoes the most changes in methylation following systemic therapy. Thirty paraffin-embedded healthy tissue samples from mastectomy specimens and blood samples from unaffected individuals will serve as normal controls.
This preliminary study can be used to determine the clinical utility of DNA methylation in breast tumor tissue and plasma as a predictive marker for response to chemotherapy and a prognostic marker for patient outcome. If a relationship is found, we can then further study if the change in methylation pattern has clinical utility in influencing therapeutic decision-making which may be further expanded to the adjuvant setting..
|Study Design||Not Provided|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Condition||Breast Tumor Tissue|
|Study Groups/Cohorts||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status||Unknown status|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
We are not actively recruiting breast cancer patients but using stored biospy and plasma samples collected in the stated Clinical Trial (Phase II study of docetaxel combined with ketoconazole in the first-line treatment of locally advanced or metastatic breast cancer patients with measurable primary breast tumor) which was already IRB-approved
For the normal controls, inclusion criteria are:
For normal controls, exclusion criteria are:
(1) Past or current history of malignancies
|Ages||21 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||Yes|
|Contacts||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries||Singapore|
|Removed Location Countries|
|Other Study ID Numbers||BR04/19/07|
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor||National University Hospital, Singapore|
|PRS Account||National University Hospital, Singapore|
|Verification Date||June 2008|