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

Memorial Sloan Kettering Cancer Center7 sites in 1 country269 target enrollmentJanuary 9, 2007

ConditionsBreast Cancer

Overview

Phase: Not Applicable
Intervention: Not specified
Conditions: Breast Cancer
Sponsor: Memorial Sloan Kettering Cancer Center
Enrollment: 269
Locations: 7
Primary Endpoint: To look for mutations in druggable oncogenic pathways in tumors progressing on anti-HER2 therapy or hormonal therapy
Status: Completed
Last Updated: 3 months ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

January 9, 2007

End Date

January 23, 2026

Last Updated

3 months ago

Study Type

Observational

Sex

All

Investigators

Sponsor

Memorial Sloan Kettering Cancer Center

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•All patients:
•Diagnosed with breast cancer.
•Patient must be able to consent to a biopsy
•Patient must be able to safely undergo a secondary biopsy, if needed.
•Patients who previously received treatment with anti-HER2 therapy (including trastuzumab, pertuzumab, TDM1, lapatinib, neratibin, or DS8201) 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+.
•Patients who previously received treatment with hormonal therapy (including aromatase inhibitors or SERMs or SERDs) 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.
•Patients not eligible for Cohorts 1 or 2.

Exclusion Criteria

•Patients who are unable to consent to a biopsy.
•Patients for whom a repeat biopsy would be medically unsafe

Outcomes

Primary Outcomes

To look for mutations in druggable oncogenic pathways in tumors progressing on anti-HER2 therapy or hormonal therapy

Time Frame: 3 years

To characterize the activity of the PI3K signaling pathway in progressive breast tumors using proteomic methods

Time Frame: 3 years

To develop new laboratory models of treatment refractory breast cancer from human tumor specimens

Time Frame: 3 years

Secondary Outcomes

To characterize the genetic heterogeneity of progressive, metastatic tumors using next generation sequencing(3 years)
To look for mutations in druggable oncogenic pathways in tumor progressing on breast cancer targeted therapies(3 years)
To evaluate dynamic proteomic changes in response to inhibition of the RTK/PI3K/ATK/mTOR pathway.(3 years)