Chemotherapy on Methylation Patterns in Breast Tumor Tissue Correlating With Clinical Response and Outcomes

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2008 by National University Hospital, Singapore.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National University Hospital, Singapore
ClinicalTrials.gov Identifier:
NCT00698477
First received: June 15, 2008
Last updated: NA
Last verified: June 2008
History: No changes posted
  Purpose

Primary Objectives

  1. To identify hypermethylated genes in paired pretreatment breast tumor tissue and plasma samples from locally advanced and metastatic breast cancer patients using a known gene panel which includes APC1, Cyclin D2, RARB, RASSF1A, Twist, Hin1 and GSTP1.

    Rationale: We and others have determined the optimal panel of genes that are able to detect free DNA in plasma and serum. We will determine if the same panel of genes is effective for detecting tumor DNA in the plasma of locally advanced and metastatic breast cancer patients. Further, to determine if the methylation profile of the plasma DNA for these genes is the same or different from the primary tumor at presentation, we will analyze the primary tumor DNA from fresh frozen samples.

  2. To identify methylation pattern changes in the same subset of patients' plasma samples at 24 hours after completion of cycle 1 of chemotherapy and within 24 hours before cycle 2.

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

Secondary Objectives

(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.


Condition
Breast Tumor Tissue

Study Type: Observational
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

Resource links provided by NLM:


Further study details as provided by National University Hospital, Singapore:

Study Start Date: October 2007
Detailed Description:

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..

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

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:

  1. Any female adult patient above 21
  2. No current or past history of underlying malignancies

Exclusion Criteria:

For normal controls, exclusion criteria are:

(1) Past or current history of malignancies

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00698477

Contacts
Contact: Sing Huang Tan, MBBS, MRCP 65-6772-1852 Sing_Huang_Tan@nuh.com.sg

Locations
Singapore
National University Hospital Recruiting
Singapore, Singapore
Contact: Sing Huang Tan, MBBS, MRCP    65-6772-1852    Sing_Huang_Tan@nuh.com.sg   
Principal Investigator: Sing Huang Tan, MBBS, MRCP         
Sponsors and Collaborators
National University Hospital, Singapore
Investigators
Principal Investigator: Sing Huang Tan, MBBS, MRCP National University Hospital, Singapore
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00698477     History of Changes
Other Study ID Numbers: BR04/19/07
Study First Received: June 15, 2008
Last Updated: June 15, 2008
Health Authority: Singapore: Domain Specific Review Boards

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on August 28, 2014