A Pharmacogenomics Study for Breast Cancer Patients Undergoing Adjuvant Chemotherapy With Doxorubicin (A)/Cyclophosphamide ©) and/or Weekly Paclitaxel

Breast Cancer Clinical Trial

Official title:

A Pharmacogenomics Study for Breast Cancer Patients Undergoing Adjuvant Chemotherapy With Doxorubicin (A)/Cyclophosphamide ©) and/or Weekly Paclitaxel

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00131963
• Other study ID #: Pro00014267
• Secondary ID: DUMC-4522-04-1-R
• Status: Completed
• Phase: N/A
• First received: August 16, 2005
• Last updated: July 22, 2016
• Start date: October 2003
• Est. completion date: October 2014

Study information

• Verified date: November 2015
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well doxorubicin, cyclophosphamide, and/or paclitaxel work in treating women with nonmetastatic breast cancer.

Description:

OBJECTIVES:

Primary

• Determine the pharmacogenomics of adjuvant chemotherapy comprising doxorubicin and cyclophosphamide and/or paclitaxel in women with nonmetastatic invasive breast cancer.

• Determine treatment-induced myelosuppression (e.g., neutropenia) in patients treated with adjuvant doxorubicin and cyclophosphamide who have polymorphisms in drug activation and metabolism genes.

• Correlate the incidence of peripheral neuropathy with pharmacogenomic analysis in patients treated with paclitaxel.

Secondary

• Determine response (i.e., relapse in the adjuvant setting) during a 10-year follow-up period in patients treated with these regimens.

OUTLINE: This is a multicenter study. Patients receive treatment on The Cancer and Leukemia Group B study(CALGB) CALGB-40101 OR are assigned to receive 1 of 2 treatment regimens on this study.

• Regimen 1: Patients receive doxorubicin IV over 10 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses.

• Regimen 2: Patients receive doxorubicin and cyclophosphamide as in regimen 1. Patients then receive paclitaxel IV over 1 hour once weekly for 12 weeks.

After completion of study treatment, patients are followed at 3, 6, and 12 months and then annually for up to 10 years.

PROJECTED ACCRUAL: A total of 500 patients (300 treated with doxorubicin and cyclophosphamide and 200 treated with paclitaxel) will be accrued for this study within 3-4 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 94
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Eligibility Criteria

• Histologically confirmed invasive breast cancer

• node negative stage > T1c or T1b with poor prognostic features (high grade, Her2/neu FISH positive, ER negative) or stage 2 (T2, N0) or

• enrolled on CALGB 40101, CALGB 49909, or the National Cancer Institute of Canada study MA-21 or

• any node positive patient or locally advanced undergoing neoadjuvant chemotherapy with either AC or paclitaxel

• Age greater than or equal to 18 years.

• >/=2 weeks from major surgery (wide excision / lumpectomy / mastectomy)

• No evidence of systemic metastasis

• Undergoing adjuvant treatment with standard dose AC or AC followed by weekly Paclitaxel at 80mg/m2

• Adequate bone marrow, hepatic and renal functions (absolute neutrophil count >1,500/ µl, platelet count > 100,000/ µl, serum creatinine <2.0 mg/dl, total Bilirubin <2.0 x the upper limit of normal (ULN)

• Ability to answer and understand study surveillance questionnaires

• No concurrent drug therapy (within 2 weeks) with agents that are known inducers or inhibitors of Cytochrome P450 (CYP450).

Exclusion Criteria

• Other anticancer cytotoxic or endocrine therapy, immunotherapy, or biologic response modifiers,Study Drugs or other concomitant medications known to cause myelosuppression especially neutropenia and neuropathy

• Eastern Cooperative Oncology Group Performance Status(ECOG) functional status > 2.

• Serious co-morbidities including poorly controlled diabetes mellitus, ischaemic heart disease,uncontrolled hypertension or active infection.

• Pregnancy

• Use of growth factor during cycle 1 of chemotherapy (AC) under pharmacokinetic evaluation

• Grade >/=2 peripheral neuropathy symptoms based on National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE) Scale. Exception: a chronic neurologic disorder will be reviewed on a case by case basis by the study PI.

• Prior treatment with weekly paclitaxelDISEASE CHARACTERISTICS:

• Histologically confirmed invasive breast cancer, meeting 1 of the following criteria:

• Node negative disease AND meets 1 of the following stage criteria:

• Primary tumor > T1c

• Primary tumor > T1b AND poor prognostic features, defined as the following:

• High-grade disease

• Human Epidermal Growth Factor Receptor 2 (HER2)/neu-positive disease by fluorescence in situ hybridization

• Estrogen receptor-negative disease

• Stage II disease (T2, N0)

• Node positive nonmetastatic disease

• Locally advanced disease AND receiving neoadjuvant chemotherapy comprising doxorubicin and cyclophosphamide OR paclitaxel

• Enrolled in clinical trial CALGB-40101

• No evidence of systemic metastasis

• Hormone receptor status:

• Not specified

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• cyclophosphamide
Given IV
• doxorubicin
Given IV
• paclitaxel
Given IV

Locations

Country	Name	City	State
United States	Duke Cancer Institute	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-induced myelosuppression (e.g., neutropenia)		12 months	No
Primary	Incidence of peripheral neuropathy		12 month	No
Secondary	Response (relapse in adjuvant setting) for 10 years after completion of study treatment		Ten years	No