Molecular Mechanisms of Clinical Resistance to Targeted Therapy Among Patients With Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2015 by Memorial Sloan Kettering Cancer Center.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center.
ClinicalTrials.gov Identifier:
NCT00897702
First received: May 9, 2009
Last updated: February 11, 2015
Last verified: February 2015

May 9, 2009
February 11, 2015
January 2007
January 2016   (final data collection date for primary outcome measure)
  • To look for mutations in druggable oncogenic pathways in tumors progressing on anti-HER2 therapy or hormonal therapy [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • To characterize the activity of the PI3K signaling pathway in progressive breast tumors using proteomic methods [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • To develop new laboratory models of treatment refractory breast cancer from human tumor specimens [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Comparison of expression levels of MUC-4 and PTEN prior to treatment with HER2-targeting agents with levels after disease progression/recurrence [ Designated as safety issue: No ]
  • Mutations relative to known HER2 sequences [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00897702 on ClinicalTrials.gov Archive Site
  • To look for mutations in druggable oncogenic pathways in tumor progressing on breast cancer targeted therapies [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • To evaluate dynamic proteomic changes in response to inhibition of the RTK/PI3K/ATK/mTOR pathway. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • To characterize the genetic heterogeneity of progressive, metastatic tumors using next generation sequencing [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Mutations in the PIK3Ca, PTEN, and epidermal growth factor receptor genes [ Designated as safety issue: No ]
  • Comparison of genome-wide expression changes in patients with disease progression after HER2-targeting agents with characteristic profiles of HER2-positive breast cancer [ Designated as safety issue: No ]
  • HER2 amplification as measured by a novel oligonucleotide microarray-based analysis [ Designated as safety issue: No ]
  • Shed HER2 extracellular domain in tumors samples obtained after disease progression/recurrence [ Designated as safety issue: No ]
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Molecular Mechanisms of Clinical Resistance to Targeted Therapy Among Patients With Breast Cancer
Molecular Mechanisms of Clinical Resistance to Targeted Therapy Among Patients With Breast Cancer

The purpose of this study is to learn why certain drugs stop working in patients.In lab studies, tumors become resistant in several ways. Specific molecules seem to change and this may be why therapy stops working. However, we do not know if the same molecules change in patients. This study is being done to see if they do change. If we learn more about how patients become resistant, we may be able to offer better treatment in the future.

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Observational
Observational Model: Case-Only
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

tissue and blood

Non-Probability Sample

Potential research subjects will be identified by a member of the patient's treatment team, the protocol investigator, or research team at Memorial Sloan-Kettering Cancer Center (MSKCC).

Breast Cancer
  • Other: Blood draw
    A single 10ml tube of blood will also be obtained for a comparison of patient's normal DNA for genomic analyses either at the time of the procedure or at a followup appointment if feasible.
  • Other: immunoenzyme technique
  • Procedure: biopsy
  • Procedure: histopathologic examination
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Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
400
January 2016
January 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

All patients:

  • Diagnosed with progressive, recurrent or metastatic HER2+ or ER+ breast cancer.

Cohort 1

  • Patients who previously received treatment with anti-HER2 therapy (including trastuzumab, pertuzumab, TDM1, or lapatinib) as part of adjuvant chemotherapy and now have progressive or recurrent breast cancer or, patients who previously (or currently) received anti-HER2 therapy as part of a regimen for metastatic breast cancer and subsequently experienced.
  • Evidence of disease progression or recurrence after prior therapy (e.g. radiologic progression by RECIST criteria or new metastasis).
  • Prior tumor biopsy (may be original) defined as HER2+ by amplification by FISH (>1.9 gene copy number) or IHC 3+.

Cohort 2

  • Patients who previously received treatment with hormonal therapy (including tamoxifen, toremifene, raloxifene, anastrozole, letrozole, exemestane, fulvestrant, ARN-810) as a part of adjuvant therapy and now have progressive or recurrent breast cancer or patients who previously (or currently) receive hormonal therapy as part of a regimen for metastatic breast cancer and subsequently experienced evidence of disease progression.

Cohort 3

  • Patients not eligible for Cohorts 1 or 2, but previously received treatment of any other kind for breast cancer.

Exclusion Criteria:

  • Patients who are unable to consent to a biopsy.
  • Patients for whom a repeat biopsy would be medically unsafe
Both
Not Provided
No
Contact: Sarat Chandarlapaty, MD 646-888-5449
Contact: Clifford Hudis, MD 646-888-5449
United States
 
NCT00897702
06-163, MSKCC-06163
Not Provided
Memorial Sloan Kettering Cancer Center.
Memorial Sloan Kettering Cancer Center.
National Cancer Institute (NCI)
Study Chair: Sarat Chandarlapaty Memorial Sloan Kettering Cancer Center.
Memorial Sloan Kettering Cancer Center.
February 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP