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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT00897702

Collaborator

National Cancer Institute (NCI) (NIH)

400

Enrollment

Locations

203.7

Duration (Months)

57.1

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Other: Blood draw Other: immunoenzyme technique Procedure: biopsy Procedure: histopathologic examination

Study Design

Study Type:

Observational

Anticipated Enrollment :

400 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

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

Study Start Date :

Jan 9, 2007

Anticipated Primary Completion Date :

Jan 1, 2024

Anticipated Study Completion Date :

Jan 1, 2024

Outcome Measures

Primary Outcome Measures

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

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]
To characterize the genetic heterogeneity of progressive, metastatic tumors using next generation sequencing [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Basking Ridge (Consent only)	Basking Ridge	New Jersey	United States	07920
2	Memorial Sloan Kettering Monmouth (Consent only)	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Bergen (Consent only)	Montvale	New Jersey	United States	07645
4	Memorial Sloan Kettering Commack (Consent only)	Commack	New York	United States	11725
5	Memoral Sloan Kettering Westchester (Consent only)	Harrison	New York	United States
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Memorial Sloan Kettering Nassau (Consent only)	Uniondale	New York	United States	11553