Breast CancerPhase 2NCT00669773
Validate Gene Expression and Proteomic Signatures Predictive of Treatment for Response for Breast Cancer Patient
A Phase 2 study testing Adriamycin and Docetaxel in people with Breast Cancer, run by National University Hospital, Singapore at 1 site in Singapore.
Trial summary
Primary Objectives 1. Validate our previously generated tumor gene expression and proteomic profiles in this independent sample to determine the predictive power to distinguish good from poor clinical and pathological responders to adriamycin or docetaxel. 2. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Adriamycin and Docetaxel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteSingapore
- Study dates
- Feb 2007to Feb 2014
- Phase
- Phase 2
- 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 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients may be included in the study only if they meet all of the following criteria:
- Female, age 18 years or above.
- Histologic or cytologic diagnosis of breast carcinoma.
- T2-4 breast cancer with measurable primary breast tumor, defined as palpable tumor with both diameters 2.0cm or greater as measured by caliper.
- Patients must not have received prior chemotherapy or hormonal therapy for the treatment of breast cancer.
- Karnofsky performance status of 70 or higher.
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- Estimated life expectancy of at least 12 weeks.
- Adequate organ function including the following:
- Bone marrow:
- Absolute neutrophil (segmented and bands) count (ANC)>= 1.5 x 10 9/L
- Platelets >= 100 x 10 9/L
- Hepatic:
- Bilirubin <= 1.5 x upper limit of normal (ULN),
- ALT or AST <= 2.5x ULN, (or <= 5 X with liver metastases)
- Renal:
- creatinine <= 1.5x ULN
- Left ventricular ejection fraction >= 50%
- Signed informed consent from patient or legal representative.
- Patients with reproductive potential must use an approved contraceptive method if appropriate (eg, intrauterine device, birth control pills, or barrier device) during and for three months after the study. Females with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.
Who cannot join
- Patients will be excluded from the study for any of the following reasons:
- Prior treatment for locally advanced or metastatic breast cancer.
- Treatment within the last 30 days with any investigational drug.
- Concurrent administration of any other tumor therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
- Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
- Pregnancy.
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- Breast feeding.
- Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
- Poorly controlled diabetes mellitus.
- Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
- Symptomatic brain metastasis.
- History of significant neurological or mental disorder, including seizures or dementia.
- Peripheral neuropathy of CTC grade 2 or above (NCI CTC version 3).
- History of hypersensitivity to drugs formulated in Tween 80, the vehicle used for commercial docetaxel formulations.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 2 Randomized Study of Adriamycin & Docetaxel in the First-line Treatment of Locally Advanced or Metastatic Breast Cancer Patients With Measurable Primary Breast Tumor to Validate Gene Expression & Proteomic Signatures Predictive of Treatment Response
Primary Objectives
- Validate our previously generated tumor gene expression and proteomic profiles in this independent sample to determine the predictive power to distinguish good from poor clinical and pathological responders to adriamycin or docetaxel.
- Validate our previously generated plasma proteomic profiles in this independent sample to determine the predictive power to distinguish good from poor clinical and pathological responders to adriamycin and docetaxel.
Read more
Secondary objectives
- To correlate adriamycin and docetaxel pharmacokinetics with
- Genetic polymorphisms of drug metabolizing enzymes and transporters, including MDR-1, Cyp3A, GSTs, and the nuclear receptors.
- Drug toxicity and tumor response.
- Peripheral mononuclear cell gene expression profiles
- To study ondansetron pharmacokinetics and correlate that with genetic polymorphisms.
Read the detailed description
Many chemotherapeutic agents are active in breast cancer, although response rate to any individual drug is only 30-50%. The choice of chemotherapy is empirical, and development of a chemosensitivity assay is desirable, to reduce costs, unnecessary toxicity, and loss of window of opportunity to cure. Single molecular markers to predict sensitivity are not highly accurate, as chemotherapy resistance mechanisms likely involve complex pathways. High-throughput technologies such as gene expression microarray and Proteinchip array allow simultaneous analysis of thousands of genes, and hundreds of proteins, and may be more informative. We previously conducted a study on patients with measurable primary breast tumor who received primary chemotherapy with an alternating regimen of adriamycin and docetaxel, and generated tumor genomic and tumor and plasma proteomic signatures that predicted for clinical and pathological response using high throughput discovery platforms. This protocol aims to recruit 20 patients as an independent test set to validate the genomic and proteomic signatures generated previously. Half the patients will be randomized to receive 4 cycles of pre-operative adriamycin (Arm A) allowing validation of the adriamycin-specific signatures, while the other half will be randomized to receive 4 cycles of pre-operative docetaxel (Arm B) allowing validation of the docetaxel-specific signatures. Subjects will then undergo resection of the primary breast tumor, followed by 4 cycles of adjuvant therapy with the alternative drug (docetaxel in Arm A, adriamycin in Arm B). Serial tumor and plasma samples will be obtained for genomic and proteomic analysis. The previously generated genomic and proteomic signatures will be applied to this independent dataset to categorize patients into good and poor responders, and the prediction correlated with actual treatment responses. Secondary goals include the correlation of patient genotype with drug pharmacokinetics, and the correlation of chemotherapy-induced peripheral blood mononuclear cell gene expression changes with treatment response and toxicities
- Conditions
- Breast Cancer
- Being tested
- Adriamycin, Docetaxel
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdriamycinDrug
Arm A: 4 cycles of adriamycin at 75mg/m2 3 weekly followed by surgery followed by 4 cycles of docetaxel at 75mg/m2 3 weekly
DocetaxelDrug
Arm B: 4 cycles of docetaxel at 75mg/m2 3 weekly followed by surgery followed by 4 cycles of adriamycin at 75mg/m2 3 weekly.
| Study group | Role | What they receive |
|---|---|---|
| Adriamycin | Experimental | Arm A: 4 cycles of adriamycin at 75mg/m2 3 weekly followed by surgery followed by 4 cycles of docetaxel at 75mg/m2 3 weekly Receives: Drug: Adriamycin |
| Docetaxel | Experimental | Not described Receives: Drug: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical and pathological response rate
Clinical and pathological response rate to four cycles of pre-operative chemotherapy.
Measured: 12 weeks
Secondary outcomes (1)
Baseline and serial changes in tumor & plasma genomic and proteomic changes
Core biopsy of breast tumor before treatment, after one cycle of pre-operative chemotherapy, and after the fourth cycle of pre-operative chemotherapy or study withdrawal for a total of 3 core biopsies.
Plasma samples for proteomics before treatment, during pre-operative chemotherapy and before surgery, before first cycle of post-operative chemotherapy, within 4 weeks after completion of 4 cycles of post-operative chemotherapy, and four monthly thereafter.
Measured: at different time-points (see description below)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2008 (estimated)
- Study startFeb 2007
- Primary completionFeb 2014 (estimated)
- Study completionFeb 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Haematology-Oncology, National University Hospital, Singapore
- Investigators
- Soo Chin LEE, MBBS, MRCP, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00669773
- Sponsor's protocol ID
- BR08/34/06
- Other IDs
- HSA No: CTC0700019, 2006/00411
- Status last verified
- Dec 2013
- First submitted
- 27 Apr 2008
- Last updated
- 10 Dec 2013
- Results posted
- No
Publications
Chang JC, Wooten EC, Tsimelzon A, Hilsenbeck SG, Gutierrez MC, Tham YL, Kalidas M, Elledge R, Mohsin S, Osborne CK, Chamness GC, Allred DC, Lewis MT, Wong H, O'Connell P. Patterns of resistance and incomplete response to docetaxel by gene expression profiling in breast cancer patients. J Clin Oncol. 2005 Feb 20;23(6):1169-77. doi: 10.1200/JCO.2005.03.156.
PubMed 15718313Petricoin EF, Ardekani AM, Hitt BA, Levine PJ, Fusaro VA, Steinberg SM, Mills GB, Simone C, Fishman DA, Kohn EC, Liotta LA. Use of proteomic patterns in serum to identify ovarian cancer. Lancet. 2002 Feb 16;359(9306):572-7. doi: 10.1016/S0140-6736(02)07746-2.
PubMed 11867112Voon PJ, Yap HL, Ma CY, Lu F, Wong AL, Sapari NS, Soong R, Soh TI, Goh BC, Lee HS, Lee SC. Correlation of aldo-ketoreductase (AKR) 1C3 genetic variant with doxorubicin pharmacodynamics in Asian breast cancer patients. Br J Clin Pharmacol. 2013 Jun;75(6):1497-505. doi: 10.1111/bcp.12021.
PubMed 23116553
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Randomized Study of Adriamycin & Docetaxel in the First-line Treatment of Locally Advanced or Metastatic Breast Cancer Patients With Measurable Primary Breast Tumor to Validate Gene Expression & Proteomic Signatures Predictive of Treatment Response
- ClinicalTrials.gov ID
- NCT00669773
- Acronym / sponsor ID
- BR08/34/06
- Conditions
- Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 49 participants (actual)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- Feb 2007
- Primary completion
- Feb 2014 (estimated)
- Study completion
- Feb 2014 (estimated)
- First posted
- 30 Apr 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
- Validate our previously generated tumor gene expression and proteomic profiles in this independent sample to determine the predictive power to distinguish good from poor clinical and pathological responders to adriamycin or docetaxel.
- Validate our previously generated plasma proteomic profiles in this independent sample to determine the predictive power to distinguish good from poor clinical and pathological responders to adriamycin and docetaxel.
Secondary objectives
- To correlate adriamycin and docetaxel pharmacokinetics with
- Genetic polymorphisms of drug metabolizing enzymes and transporters, including MDR-1, Cyp3A, GSTs, and the nuclear receptors.
- Drug toxicity and tumor response.
- Peripheral mononuclear cell gene expression profiles
- To study ondansetron pharmacokinetics and correlate that with genetic polymorphisms.
Detailed description
Many chemotherapeutic agents are active in breast cancer, although response rate to any individual drug is only 30-50%. The choice of chemotherapy is empirical, and development of a chemosensitivity assay is desirable, to reduce costs, unnecessary toxicity, and loss of window of opportunity to cure. Single molecular markers to predict sensitivity are not highly accurate, as chemotherapy resistance mechanisms likely involve complex pathways. High-throughput technologies such as gene expression microarray and Proteinchip array allow simultaneous analysis of thousands of genes, and hundreds of proteins, and may be more informative. We previously conducted a study on patients with measurable primary breast tumor who received primary chemotherapy with an alternating regimen of adriamycin and docetaxel, and generated tumor genomic and tumor and plasma proteomic signatures that predicted for clinical and pathological response using high throughput discovery platforms. This protocol aims to recruit 20 patients as an independent test set to validate the genomic and proteomic signatures generated previously. Half the patients will be randomized to receive 4 cycles of pre-operative adriamycin (Arm A) allowing validation of the adriamycin-specific signatures, while the other half will be randomized to receive 4 cycles of pre-operative docetaxel (Arm B) allowing validation of the docetaxel-specific signatures. Subjects will then undergo resection of the primary breast tumor, followed by 4 cycles of adjuvant therapy with the alternative drug (docetaxel in Arm A, adriamycin in Arm B). Serial tumor and plasma samples will be obtained for genomic and proteomic analysis. The previously generated genomic and proteomic signatures will be applied to this independent dataset to categorize patients into good and poor responders, and the prediction correlated with actual treatment responses. Secondary goals include the correlation of patient genotype with drug pharmacokinetics, and the correlation of chemotherapy-induced peripheral blood mononuclear cell gene expression changes with treatment response and toxicities
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Adriamycin | Experimental | Drug: AdriamycinArm A: 4 cycles of adriamycin at 75mg/m2 3 weekly followed by surgery followed by 4 cycles of docetaxel at 75mg/m2 3 weekly |
| Docetaxel | Experimental | Drug: Docetaxel |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Female, age 18 years or above.
- Histologic or cytologic diagnosis of breast carcinoma.
- T2-4 breast cancer with measurable primary breast tumor, defined as palpable tumor with both diameters 2.0cm or greater as measured by caliper.
- Patients must not have received prior chemotherapy or hormonal therapy for the treatment of breast cancer.
- Karnofsky performance status of 70 or higher.
Key exclusion criteria (14 listed)
- Prior treatment for locally advanced or metastatic breast cancer.
- Treatment within the last 30 days with any investigational drug.
- Concurrent administration of any other tumor therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
- Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
- Pregnancy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AdriamycinArm A: 4 cycles of adriamycin at 75mg/m2 3 weekly followed by surgery followed by 4 cycles of docetaxel at 75mg/m2 3 weekly | Drug | Adriamycin |
| DocetaxelArm B: 4 cycles of docetaxel at 75mg/m2 3 weekly followed by surgery followed by 4 cycles of adriamycin at 75mg/m2 3 weekly. | Drug | Docetaxel |
Primary outcome
Clinical and pathological response rate
Time frame: 12 weeks
Clinical and pathological response rate to four cycles of pre-operative chemotherapy.
1 secondary outcome
Baseline and serial changes in tumor & plasma genomic and proteomic changes
Time frame: at different time-points (see description below)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2013.
- Background: PubMed 15718313Chang JC, Wooten EC, Tsimelzon A, Hilsenbeck SG, Gutierrez MC, Tham YL, Kalidas M, Elledge R, Mohsin S, Osborne CK, Chamness GC, Allred DC, Lewis MT, Wong H, O'Connell P. Patterns of resistance and incomplete response to docetaxel by gene expression profiling in breast cancer patients. J Clin Oncol. 2005 Feb 20;23(6):1169-77. doi: 10.1200/JCO.2005.03.156.
- Background: PubMed 11867112Petricoin EF, Ardekani AM, Hitt BA, Levine PJ, Fusaro VA, Steinberg SM, Mills GB, Simone C, Fishman DA, Kohn EC, Liotta LA. Use of proteomic patterns in serum to identify ovarian cancer. Lancet. 2002 Feb 16;359(9306):572-7. doi: 10.1016/S0140-6736(02)07746-2.
- Derived from this study: PubMed 23116553Voon PJ, Yap HL, Ma CY, Lu F, Wong AL, Sapari NS, Soong R, Soh TI, Goh BC, Lee HS, Lee SC. Correlation of aldo-ketoreductase (AKR) 1C3 genetic variant with doxorubicin pharmacodynamics in Asian breast cancer patients. Br J Clin Pharmacol. 2013 Jun;75(6):1497-505. doi: 10.1111/bcp.12021.
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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.
Soo Chin LEE, 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?
A Phase 2 study testing Adriamycin and Docetaxel in people with Breast Cancer, 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 19 inclusion and 14 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 10 Dec 2013. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical and pathological response rate (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00669773, which also lists 3 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 10 Dec 2013.