AzTrials
AzTrials

Metastatic Breast CancerPhase 2NCT00212082

Gene Expression Profiles in Predicting Chemotherapy Response in Breast Cancer

A Phase 2 study testing doxorubicin, docetaxel in people with Metastatic Breast Cancer, run by National University Hospital, Singapore at 1 site in Singapore.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

We hypothesize that changes in tumor gene expression profiles vary in response to different sequences and types of chemotherapy, and that gene expression changes will correlate with tumor response. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Metastatic Breast Cancer
What is being tested?
doxorubicin, docetaxel
How many people
100 participants
Where
1 siteSingapore
Study dates
Apr 2002to not given
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

  • Female, age > 18 years.
  • Histologic or cytologic diagnosis of breast carcinoma.
  • Stage II to IV 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.
  • Estimated life expectancy of at least 12 weeks.
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  • Adequate organ function including the following:
  • Bone marrow: White blood cells (WBC) >= 3.5 x 109/L Absolute neutrophil (segmented and bands) count (ANC) >= 1.5 x 109/L Platelets >= 100 x 109/L Haemoglobin >= 9g/dL
  • Hepatic: Bilirubin <= 1.5 x upper limit of normal (ULN), ALT or AST <= 2.5x ULN, (or <=5 X with liver metastases) Alkaline phosphatase <= 2.5x ULN.
  • Renal: creatinine <= 1.5x ULN
  • Cardiac:
  • Adequate cardiac function
  • 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

  • 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.
  • Breast feeding.
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  • 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.
  • 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.

Singapore1 site

  • National University Hospital

    Singapore

Other trials in Singapore

About this study

Official title: Gene Expression Profiles of Breast Cancer Treated With Sequential Adriamycin and Docetaxel in Relation to Tumor Responses

We hypothesize that changes in tumor gene expression profiles vary in response to different sequences and types of chemotherapy, and that gene expression changes will correlate with tumor response. We are also looking to correlate drug pharmacokinetics and treatment toxicity with genotype of drug metabolizing enzymes and tranporters.Patients with metastatic breast cancer and who have measurable primary breast tumor will be randomized to one of two alternating sequences of adriamycin and docetaxel. Serial tumor biopsies and plasma samples will be obtained for gene expression and proteomic studies to identify biomarkers that will predict for chemotherapy response.

Read the detailed description

Significant inter-individual variation exists in tumor response and chemotherapy toxicity because of unique tumor and patient factors. Individual drugs with distinct mechanisms of action may induce specific genomic and proteomic changes that may be used as predictor for response. We plan to study serial genomic and proteomic profiles in primary breast tumor treated with one of two sequences of alternating adriamycin (A) and docetaxel (T), A>T>A>T>A>T, or T>A>T>A>T>A, at 75mg/m2 3 weekly for each drug. Pharmacokinetic analysis of both drugs will be performed; amplified tumor RNA will be hybridized on Affymetrix® HG-U133+2 array; tumor proteins will be fractionated and profiled with ProteinChip® Array SELDI MS (Ciphergen). Tumor gene expression and proteomic changes will be correlated with treatment response to identify biomarkers that may predict chemotherapy sensitivity.

Being tested
doxorubicin, docetaxel
Keywords
breast cancer, chemotherapy response, gene expression profiles, proteomics
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • doxorubicin, docetaxelDrug

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 1. Evaluate the impact of adriamycin and docetaxel on tumor gene expression profiles.

  2. 2. Correlate overall tumor response with tumor gene expression profiles.

Secondary outcomes (3)

  1. To correlate adriamycin and docetaxel pharmacokinetics with:

  2. 1. Genetic polymorphisms of MDR-1, Cyp3A and GSTs.

  3. 2. Drug toxicity and tumor response.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Sep 2005 (estimated)
  2. Study startApr 2002

Resources

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
Single group
Masking
None (open label)
Enrolment
100 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00212082
Sponsor's protocol ID
HO B17/02
Status last verified
Jun 2008
First submitted
13 Sep 2005
Last updated
12 Jun 2008
Results posted
No

Publications

  • Tan SH, Sapari NS, Miao H, Hartman M, Loh M, Chng WJ, Iau P, Buhari SA, Soong R, Lee SC. High-Throughput Mutation Profiling Changes before and 3 Weeks after Chemotherapy in Newly Diagnosed Breast Cancer Patients. PLoS One. 2015 Dec 2;10(12):e0142466. doi: 10.1371/journal.pone.0142466. eCollection 2015.

    PubMed 26630576

  • Voon 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

  • Chuah BY, Putti T, Salto-Tellez M, Charlton A, Iau P, Buhari SA, Wong CI, Tan SH, Wong AL, Chan CW, Goh BC, Lee SC. Serial changes in the expression of breast cancer-related proteins in response to neoadjuvant chemotherapy. Ann Oncol. 2011 Aug;22(8):1748-54. doi: 10.1093/annonc/mdq755. Epub 2011 Feb 25.

    PubMed 21355070

  • Lim YW, Goh BC, Wang LZ, Tan SH, Chuah BYS, Lim SE, Iau P, Buhari SA, Chan CW, Sukri NB, Cordero MT, Soo R, Lee SC. Pharmacokinetics and pharmacodynamics of docetaxel with or without ketoconazole modulation in chemonaive breast cancer patients. Ann Oncol. 2010 Nov;21(11):2175-2182. doi: 10.1093/annonc/mdq230. Epub 2010 Apr 29.

    PubMed 20430905

  • Lee SC, Xu X, Chng WJ, Watson M, Lim YW, Wong CI, Iau P, Sukri N, Lim SE, Yap HL, Buhari SA, Tan P, Guo J, Chuah B, McLeod HL, Goh BC. Post-treatment tumor gene expression signatures are more predictive of treatment outcomes than baseline signatures in breast cancer. Pharmacogenet Genomics. 2009 Nov;19(11):833-42. doi: 10.1097/FPC.0b013e328330a39f.

    PubMed 19809382

  • Fan L, Goh BC, Wong CI, Sukri N, Lim SE, Tan SH, Guo JY, Lim R, Yap HL, Khoo YM, Iau P, Lee HS, Lee SC. Genotype of human carbonyl reductase CBR3 correlates with doxorubicin disposition and toxicity. Pharmacogenet Genomics. 2008 Jul;18(7):621-31. doi: 10.1097/FPC.0b013e328301a869.

    PubMed 18551042

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing doxorubicin, docetaxel in people with Metastatic 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 14 inclusion and 13 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: finished, as of the sponsor's last update on 12 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.

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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

1. Evaluate the impact of adriamycin and docetaxel on tumor gene expression profiles.. The study lists 2 primary outcomes in all. 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 NCT00212082, which also lists 6 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 12 Jun 2008.

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