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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

Brief Summary:

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.


Condition or disease Intervention/treatment
Breast Cancer Genetic: gene expression analysis Genetic: polymerase chain reaction Other: laboratory biomarker analysis

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Detailed Description:

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.


Study Type : Observational
Estimated Enrollment : 3677 participants
Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: Intrinsic Breast Cancer Subtypes and Benefit of Paclitaxel in CALGB 9344 and Dose Dense Therapy in CALGB 9741
Study Start Date : April 2009
Actual Primary Completion Date : May 2010
Actual Study Completion Date : February 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Paclitaxel

Group/Cohort Intervention/treatment
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.
Genetic: gene expression analysis
Genetic: polymerase chain reaction
Other: laboratory biomarker analysis



Primary Outcome Measures :
  1. Disease-free survival (DFS) [ Time Frame: Up to 10 years ]

Secondary Outcome Measures :
  1. 5- and 10-year DFS rates [ Time Frame: Up to 10 years ]
  2. Overall survival [ Time Frame: Up to 10 years ]

Biospecimen Retention:   Samples With DNA
Tumor tissue samples


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients diagnosed with breast cancer previously treated with paclitaxel and enrolled on CALGB-9344 or CALGB-9741.
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00991263


Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Study Chair: Matthew J. Ellis, MD, PhD, FRCP Washington University Siteman Cancer Center

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00991263     History of Changes
Other Study ID Numbers: CALGB-159905C-ICSC
CALGB-159905C-ICSC
CDR0000647570 ( Registry Identifier: NCI Physician Data Query )
First Posted: October 7, 2009    Key Record Dates
Last Update Posted: August 8, 2017
Last Verified: August 2017

Keywords provided by Alliance for Clinical Trials in Oncology:
stage II breast cancer
stage IIIA breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action