Clinical trial NCT00897702: Molecular Mechanisms of Clinical Resistance to Targeted Therapy Among Patients With Breast Cancer
Official title: Molecular Mechanisms of Clinical Resistance to Targeted Therapy Among Patients With Breast Cancer
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Breast Cancer
Keywords: recurrent breast cancer
male breast cancer
stage IV breast cancer
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-05-12
Enrollment: 269
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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).

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.


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.

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

Primary outcomes:
measure: To look for mutations in druggable oncogenic pathways in tumors progressing on anti-HER2 therapy or hormonal therapy
timeFrame: 3 years
measure: To characterize the activity of the PI3K signaling pathway in progressive breast tumors using proteomic methods
timeFrame: 3 years
measure: To develop new laboratory models of treatment refractory breast cancer from human tumor specimens
timeFrame: 3 years
Secondary outcomes:
measure: To look for mutations in druggable oncogenic pathways in tumor progressing on breast cancer targeted therapies
timeFrame: 3 years
measure: To evaluate dynamic proteomic changes in response to inhibition of the RTK/PI3K/ATK/mTOR pathway.
timeFrame: 3 years
measure: To characterize the genetic heterogeneity of progressive, metastatic tumors using next generation sequencing
timeFrame: 3 years
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge (Consent only)
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth (Consent only)
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen (Consent only)
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack (Consent only)
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester (Consent only)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau (Consent only)
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Sarat Chandarlapaty, MD, PhD
role: STUDY_CHAIR
References: