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
  Purpose

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.


Condition Intervention
Breast Cancer
Other: Blood draw
Other: immunoenzyme technique
Procedure: biopsy
Procedure: histopathologic examination

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Molecular Mechanisms of Clinical Resistance to Targeted Therapy Among Patients With Breast Cancer

Resource links provided by NLM:


Further study details as provided by Memorial Sloan Kettering Cancer Center:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Biospecimen Retention:   Samples With DNA

tissue and blood


Estimated Enrollment: 400
Study Start Date: January 2007
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Intervention Details:
    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
  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

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).

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00897702

Contacts
Contact: Sarat Chandarlapaty, MD 646-888-5449
Contact: Clifford Hudis, MD 646-888-5449

Locations
United States, New Jersey
Memorial Sloan Kettering at Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Sarat Chandarlapaty, MD    646-888-5449      
United States, New York
Memorial Sloan Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Sarat Chandarlapaty, MD    646-888-5449      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Sarat Chandarlapaty, MD    646-888-5449      
Memorial Sloan Kettering Cancer Center at Mercy Medical Center Recruiting
Rockville Centre, New York, United States, 11570
Contact: Sarat Chandarlapaty, MD    646-888-5449      
Memoral Sloan Kettering Cancer Center@Phelps Recruiting
Sleepy Hollow, New York, United States
Contact: Sarat Chandarlapaty, MD    646-888-5449      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
Study Chair: Sarat Chandarlapaty Memorial Sloan Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00897702     History of Changes
Other Study ID Numbers: 06-163, MSKCC-06163
Study First Received: May 9, 2009
Last Updated: February 11, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan Kettering Cancer Center:
recurrent breast cancer
male breast cancer
stage IV breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases

ClinicalTrials.gov processed this record on May 21, 2015