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Study of Tissue Samples From Women Treated With Paclitaxel for Breast Cancer on Clinical Trial CALGB-9344 or CALGB-9741

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ClinicalTrials.gov Identifier: NCT00991263
Recruitment Status : Completed
First Posted : October 7, 2009
Last Update Posted : August 8, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

October 6, 2009
October 7, 2009
August 8, 2017
April 2009
May 2010   (Final data collection date for primary outcome measure)
Disease-free survival (DFS) [ Time Frame: Up to 10 years ]
Disease-free survival (DFS)
Complete list of historical versions of study NCT00991263 on ClinicalTrials.gov Archive Site
  • 5- and 10-year DFS rates [ Time Frame: Up to 10 years ]
  • Overall survival [ Time Frame: Up to 10 years ]
  • 5- and 10-year DFS rates
  • Overall survival
Not Provided
Not Provided
 
Study of Tissue Samples From Women Treated With Paclitaxel for Breast Cancer on Clinical Trial CALGB-9344 or CALGB-9741
Intrinsic Breast Cancer Subtypes and Benefit of Paclitaxel in CALGB 9344 and Dose Dense Therapy in CALGB 9741

RATIONALE: Studying the genes expressed in samples of tumor tissue from patients with cancer may help doctors identify biomarkers related to cancer.

PURPOSE: This research study is looking at tissue samples from women treated with paclitaxel for breast cancer on clinical trial CALGB 9344 or CALGB 9741.

OBJECTIVES:

Primary

  • To determine whether subtype-specific treatment effects correlate with disease-free survival (DFS), as determined by a significant interaction between PAM50-based intrinsic subtypes, and (a) paclitaxel benefit in CLB-9344 and (b) dose density in CALGB-9741.
  • To determine whether subtype-specific treatment effects correlate with DFS for the HER2-negative subsets in CALGB-9344 and CALGB-9741, as determined by analysis of tissue microarray (TMA) and slides.
  • To determine the relationship between PAM50-defined risk of relapse (ROR) score and DFS in CALGB-9344 and CALGB-9741.
  • To evaluate the relationship between PAM50-defined ROR score and DFS in the HER2-negative subsets in CALGB-9344 and CALGB-9741, as determined by analysis of TMA and slides.
  • To examine the relationship between PAM50-defined proliferation score and DFS in CALGB-9344 and CALGB-9741 in multivariate Cox-proportional hazards models including the following covariates: (a) number of positive lymph nodes, square root transformation; (b) menopausal status (pre versus peri/post); CALGB-9344 only; c) dose of doxorubicin hydrochloride (60/75/90 mg/m^2); and CALGB-9741 only; and (d) sequence of treatment.

Secondary

  • To evaluate overall survival (OS) in a Cox-proportional hazards-regression model for testing the interaction between ROR with (a) paclitaxel benefit in CALGB-9344 and (b) dose density in CALGB-9741.
  • To test for a significant interaction between ROR and paclitaxel benefit at 5-year and 10-year DFS.
  • To test whether 5-year and 10-year DFS rates can be associated to a significant interaction between the proliferation score with (a) paclitaxel benefit in CALGB-9344 and (b) dose density in CALGB-9741.

OUTLINE: Tissue blocks from CALGB-9344 and CALGB-9741 are utilized to purify RNA to be tested in the PAM50 assay (a 50-gene quantitative PCR assay, that provides an intrinsic breast cancer subtype diagnosis) and generate risk of relapse (ROR) scores.

The assay identifies five subtypes with the following characteristics:

  • Luminal A: This subtype expresses estrogen receptor (ER) accompanied by high levels of ER-associated gene expression. Genes associated with cell cycle activation are not highly expressed and this tumor type is only very rarely HER2+. This subgroup has the most favorable prognosis and is enriched for endocrine therapy responsive tumors.
  • Luminal B: This subtype expresses ER and ER-associated gene expression but to a lower extent. Genes associated with cell cycle activation are highly expressed and this tumor type can be HER2+ (~20%) or HER2- thus, from the clinical perspective, Luminal B tumors are at least two further subtypes defined by the presence or absence of HER2-gene amplification. The prognosis is unfavorable (despite ER expression) and endocrine therapy responsiveness is generally diminished.
  • Basal-like: This subtype is ER-, is almost always clinically HER2- and expresses a suite of "basal" biomarkers. Genes associated with cell cycle activation are highly expressed.
  • HER2-enriched: This subtype is ER- and is HER2+ in the majority of cases. Genes associated with cell cycle activation are highly expressed and these tumors have a poor outcome. Tumors within this classification that are clinically HER2- fall into a class previously described as double-negative non-basal.
  • Normal-like: A tumor subtype diagnosis cannot be provided from samples that exhibit a normal-like profile. Since this profile was trained on samples without cancer, "normal-like" implies there are too few tumor cells in the sample to make a true tumor subtype diagnosis.

PROJECTED ACCRUAL: A total of 2,245 tissue blocks from CALGB-9544 and 1,432 tissue blocks from CALGB-9741 will be accrued for this study.

Observational
Observational Model: Case-Only
Time Perspective: Retrospective
Not Provided
Retention:   Samples With DNA
Description:
Tumor tissue samples
Non-Probability Sample
Patients diagnosed with breast cancer previously treated with paclitaxel and enrolled on CALGB-9344 or CALGB-9741.
Breast Cancer
  • Genetic: gene expression analysis
  • Genetic: polymerase chain reaction
  • Other: laboratory biomarker analysis
Group 1
Tissue blocks from CALGB-9344 and CALGB-9741 are utilized to purify RNA to be tested in the PAM50 assay (a 50-gene quantitative PCR assay, that provides an intrinsic breast cancer subtype diagnosis) and generate risk of relapse (ROR) scores. For more information, see Details section.
Interventions:
  • Genetic: gene expression analysis
  • Genetic: polymerase chain reaction
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
3677
Same as current
February 2012
May 2010   (Final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Diagnosis of stage II or IIIA breast cancer

    • Received treatment with paclitaxel on clinical trial CALGB-9344 or CALGB-9741
  • Tissue blocks available

PATIENT CHARACTERISTICS:

  • See Disease Characteristics
  • Pre-, peri-, or postmenopausal

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
Sexes Eligible for Study: Female
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
 
NCT00991263
CALGB-159905C-ICSC
CALGB-159905C-ICSC
CDR0000647570 ( Registry Identifier: NCI Physician Data Query )
No
Not Provided
Not Provided
Alliance for Clinical Trials in Oncology
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Study Chair: Matthew J. Ellis, MD, PhD, FRCP Washington University Siteman Cancer Center
Alliance for Clinical Trials in Oncology
August 2017