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

Active, not recruiting

• Conditions: Breast Cancer

• Registration Number: NCT00897702
• Lead Sponsor: Memorial Sloan Kettering Cancer Center

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2007-01-09
• Study First Submitted: 2009-05-09
• Study First Submitted QC: 2009-05-09
• Study First Posted: 2009-05-12
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-07
• Last Update Posted: 2024-11-11
• Primary Completion: 2025-01
• Study Completion: 2025-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 269

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.

Cohort 1

• 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+.

Cohort 2

• 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.

Cohort 3

• Patients not eligible for Cohorts 1 or 2.

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Exclusion Criteria

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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To look for mutations in druggable oncogenic pathways in tumors progressing on anti-HER2 therapy or hormonal therapy	3 years
To characterize the activity of the PI3K signaling pathway in progressive breast tumors using proteomic methods	3 years
To develop new laboratory models of treatment refractory breast cancer from human tumor specimens	3 years

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (7)

Memorial Sloan Kettering Monmouth (Consent only); 🇺🇸 Middletown, New Jersey, United States

Memorial Sloan Kettering Nassau (Consent only); 🇺🇸 Uniondale, New York, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Commack (Consent only); 🇺🇸 Commack, New York, United States

Memorial Sloan Kettering Basking Ridge (Consent only); 🇺🇸 Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Bergen (Consent only); 🇺🇸 Montvale, New Jersey, United States

Memorial Sloan Kettering Westchester (Consent only); 🇺🇸 Harrison, New York, United States