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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00897702
• Other study ID #: 06-163
• Secondary ID: MSKCC-06163
• Status: Active, not recruiting
• Start date: January 9, 2007
• Est. completion date: January 2025

Study information

• Verified date: February 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 269
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Exclusion Criteria:

• Patients who are unable to consent to a biopsy.

• Patients for whom a repeat biopsy would be medically unsafe

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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.
• immunoenzyme technique

Procedure:
• biopsy

• histopathologic examination

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge (Consent only)	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Commack (Consent only)	Commack	New York
United States	Memorial Sloan Kettering Westchester (Consent only)	Harrison	New York
United States	Memorial Sloan Kettering Monmouth (Consent only)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (Consent only)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Nassau (Consent only)	Uniondale	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To look for mutations in druggable oncogenic pathways in tumors progressing on anti-HER2 therapy or hormonal therapy		3 years
Primary	To characterize the activity of the PI3K signaling pathway in progressive breast tumors using proteomic methods		3 years
Primary	To develop new laboratory models of treatment refractory breast cancer from human tumor specimens		3 years
Secondary	To look for mutations in druggable oncogenic pathways in tumor progressing on breast cancer targeted therapies		3 years
Secondary	To evaluate dynamic proteomic changes in response to inhibition of the RTK/PI3K/ATK/mTOR pathway.		3 years
Secondary	To characterize the genetic heterogeneity of progressive, metastatic tumors using next generation sequencing		3 years

External Links

•   Memorial Sloan Kettering Cancer Center