Breast Tumor TissueNCT00698477
Chemotherapy on Methylation Patterns in Breast Tumor Tissue Correlating With Clinical Response and Outcomes
An observational study of Breast Tumor Tissue, run by National University Hospital, Singapore at 1 site in Singapore.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Breast Tumor Tissue
- How many people
- Not given
- Where
- 1 siteSingapore
- Study dates
- Oct 2007to not given
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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:
- Any female adult patient above 21
- No current or past history of underlying malignancies
Who cannot join
- For normal controls, exclusion criteria are:
- Past or current history of malignancies
Trial locations and contacts
1 site in 1 country.
Singapore1 site, 1 recruiting
- Recruiting
National University Hospital
Singapore
Sing Huang Tan, MBBS, MRCP, 65-6772-1852, Sing_Huang_Tan@nuh.com.sg
Sing Huang Tan, MBBS, MRCP
About this study
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
Primary Objectives
- 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.
- 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.
Read more
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.
Read the 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..
- Conditions
- Breast Tumor Tissue
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2008 (estimated)
- Study startOct 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast Tumor TissueStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Investigators
- Sing Huang Tan, MBBS, MRCP, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00698477
- Sponsor's protocol ID
- BR04/19/07
- Status last verified
- Jun 2008
- First submitted
- 15 Jun 2008
- Last updated
- 17 Jun 2008
- Results posted
- No
Publications
Fackler MJ, McVeigh M, Mehrotra J, Blum MA, Lange J, Lapides A, Garrett E, Argani P, Sukumar S. Quantitative multiplex methylation-specific PCR assay for the detection of promoter hypermethylation in multiple genes in breast cancer. Cancer Res. 2004 Jul 1;64(13):4442-52. doi: 10.1158/0008-5472.CAN-03-3341.
PubMed 15231653Swift-Scanlan T, Blackford A, Argani P, Sukumar S, Fackler MJ. Two-color quantitative multiplex methylation-specific PCR. Biotechniques. 2006 Feb;40(2):210-9. doi: 10.2144/000112097.
PubMed 16526411
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00698477
- Acronym / sponsor ID
- BR04/19/07
- Conditions
- Breast Tumor Tissue
- Study type
- Observational
- Recruitment status
- Unknown status
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- Oct 2007
- First posted
- 17 Jun 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objectives
- 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.
- 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.
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..
Study design
Who may qualify
- Ages
- 21 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
- Any female adult patient above 21
- No current or past history of underlying malignancies
Key exclusion criteria (2 listed)
- Past or current history of malignancies
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2008.
- Background: PubMed 15231653Fackler MJ, McVeigh M, Mehrotra J, Blum MA, Lange J, Lapides A, Garrett E, Argani P, Sukumar S. Quantitative multiplex methylation-specific PCR assay for the detection of promoter hypermethylation in multiple genes in breast cancer. Cancer Res. 2004 Jul 1;64(13):4442-52. doi: 10.1158/0008-5472.CAN-03-3341.
- Background: PubMed 16526411Swift-Scanlan T, Blackford A, Argani P, Sukumar S, Fackler MJ. Two-color quantitative multiplex methylation-specific PCR. Biotechniques. 2006 Feb;40(2):210-9. doi: 10.2144/000112097.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sing Huang Tan, MBBS, MRCP principal investigator
National University Hospital, Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Tumor Tissue, run by National University Hospital, Singapore at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Jun 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sing Huang Tan, MBBS, MRCP (65-6772-1852, Sing_Huang_Tan@nuh.com.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00698477, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2008.