Validate Gene Expression and Proteomic Signatures Predictive of Treatment for Response for Breast Cancer Patient

NCT00669773 | Unknown Phase 2

• 3 other identifiers: BR08/34/06HSA No: CTC07000192006/00411
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objectives

1. 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. 2.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.
3. 3.To correlate adriamycin and docetaxel pharmacokinetics with
4. 4.Genetic polymorphisms of drug metabolizing enzymes and transporters, including MDR-1, Cyp3A, GSTs, and the nuclear receptors.
5. 5.Drug toxicity and tumor response.
6. 6.Peripheral mononuclear cell gene expression profiles
7. 7.To study ondansetron pharmacokinetics and correlate that with genetic polymorphisms.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Clinical and pathological response rate

  Clinical and pathological response rate to four cycles of pre-operative chemotherapy.

  12 weeks

Secondary Outcomes (1)

• Baseline and serial changes in tumor & plasma genomic and proteomic changes

  at different time-points (see description below)

Study Arms (2)

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

Drug: Adriamycin

Docetaxel

EXPERIMENTAL

Drug: Docetaxel

Interventions

Adriamycin DRUG

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

Adriamycin

Docetaxel DRUG

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.

Docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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:

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital

Singapore, Singapore

Location

Related Publications (3)

• 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.

  PMID: 15718313 BACKGROUND

• Petricoin 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.

  PMID: 11867112 BACKGROUND

• 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.

  PMID: 23116553 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Doxorubicin; Docetaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Study Officials

• Soo Chin LEE, MBBS, MRCP

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Lee Soo Chin

Study Record Dates

• First Submitted: April 27, 2008
• First Posted: April 30, 2008
• Study Start: February 1, 2007
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: December 10, 2013

Record last verified: 2013-12

Locations

SG (1)