Genetic Analysis in Blood and Tumor Samples From Patients With Advanced or Metastatic Estrogen Receptor Positive and HER2 Negative Breast Cancer Receiving Palbociclib and Endocrine Therapy

NCT03281902 | Active Not Recruiting

• 4 other identifiers: MC1634NCI-2017-01479P50CA16850417-002697
• Study Type: observational
• Target: 68
• Locations: 1 country
• Sites: 3

Brief Summary

This research trial studies genetic profiles in blood and tumor samples from patients with estrogen receptor positive and HER2 negative breast cancer that has spread to other places in the body who are receiving palbociclib and endocrine therapy. Examining the genetic changes associated with the cancer and comparing the genetic material from the cancer tissue with the genetic material found in the blood may help doctors to develop customized treatment for breast cancer.

Conditions

Advanced Breast Carcinoma; Locally Advanced Breast Carcinoma; Metastatic Breast Carcinoma; Recurrent Breast Carcinoma; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IV Breast Cancer AJCC v6 and v7

Outcome Measures

Primary Outcomes (1)

• Bioinformatics analysis

  Next-generation sequencing data will be used to identify variants associated with the progression free survival. Pathology analysis will also be performed.

  Up to 3 years

Secondary Outcomes (5)

• Ki67 and TK1 changes

  after 2 months of treatment

• Changes in EMT markers (including Vimentin, SLUG and E-cadherin) and tumor infiltrating lymphocytes (TILs) (including CD8, PD-L1, and FOXP3)

  after 2 months of treatment

• Changes in serum TK1 levels

  After 2 months of treatment

• Change in phenotype of Ki67 and serum TK1 levels

  After 2 months of treatment

• Differences between those with and without a blood draw taken

  After 2 months of treatment

Study Arms (1)

Ancillary-Correlative (genetic profile analysis)

Patents undergo collection of blood and stool samples at baseline, 7 days after letrozole monotherapy treatment, and at completion of each cycle, urine samples at baseline and completion of each cycle, and saliva samples at baseline. Patients also undergo collection of blood and urine samples at disease progression. Biopsy samples are analyzed for genetic profile via genome sequencing and RNA sequencing. Biopsy samples are also used for the generation of xenograft mice model.

Procedure: Biopsy; Procedure: Biospecimen Collection; Other: Laboratory Biomarker Analysis

Interventions

Biopsy PROCEDURE

Undergo tumor biopsy

Also known as: BIOPSY_TYPE, Bx

Ancillary-Correlative (genetic profile analysis)

Biospecimen Collection PROCEDURE

Undergo collection of blood, urine, stool, and saliva

Ancillary-Correlative (genetic profile analysis)

Laboratory Biomarker Analysis OTHER

Correlative studies

Ancillary-Correlative (genetic profile analysis)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Women who have disease that is amenable to biopsy and agree to undergo a standard of care core biopsy of recurrent or metastatic breast cancer, and to collect additional core samples for research purposes

You may qualify if:

• Women who have disease that is amenable to biopsy and agree to undergo a standard of care and /or research biopsy
• Note: If a standard of care biopsy was recently obtained =\< 2 months of pre-registration, eligible patients should agree to a research biopsy of recurrent or metastatic breast cancer prior to the start of protocol treatment to collect additional core samples for research purposes
• Patients must satisfy one of the following criteria for prior therapy:
• First line setting: No prior endocrine therapy in the metastatic setting with no more than one prior line of chemotherapy in the advanced/metastatic setting
• Second line setting: Progression on one prior line of endocrine based therapy monotherapy either in the adjuvant or advanced/metastatic setting; either one or two prior lines of chemotherapy in the advanced setting are allowed
• Note: Patients receiving bisphosphonate or denosumab therapy prior to registration may continue at the same intervals used prior to study registration
• First line therapy setting only: The intention to begin palbociclib and letrozole as treatment for locally advanced or metastatic breast cancer
• Second line therapy setting only: The intention to begin palbociclib and fulvestrant as treatment for metastatic breast cancer (after progression on first line endocrine therapy)
• Note: Patients who are to receive second line endocrine therapy are allowed to remain on their most recent treatment (tamoxifen or an aromatase inhibitor during the pre-registration period as well as after registration while awaiting insurance approval for the use of palbociclib
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria or bone only disease are eligible.
• Note: Those patients with both non-measurable disease and bone metastases are eligible
• Note: Patients are not allowed to begin a new systemic anti-cancer therapy during pre-registration with the exception of bisphosphonate or denosumab; palliative radiation to lesions that will not be biopsied or used for assessing disease response (target lesions) is allowed during pre-registration
• No current evidence of visceral crisis
• History of central nervous system metastasis are allowed provided they have been treated (i.e., surgery, radiation, and/or radiosurgery) \>= 12 weeks prior to pre-registration and have stable neurologic function, including no requirement for medication(s) to control symptoms for at least 2 weeks; Note: patients with known leptomeningeal disease are not eligible
• Women who are premenopausal must agree to begin or continue an leutinizing hormone releasing hormone (LHRH) agonist (goserelin preferred)

You may not qualify if:

• History of metastatic ER negative or HER2 positive breast cancer
• Prior treatment in the metastatic setting with everolimus, or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway
• Uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Uncontrolled symptomatic cardiac arrhythmia
• Uncontrolled hypertension (defined as blood pressure \> 160/90)
• Other active second malignancy other than non-melanoma skin cancers =\< 3 years of pre-registration; Note: a second malignancy is not considered active if all treatment for that malignancy is completed and the patient has been disease-free for =\< 3 years prior to pre-registration
• Prior hematopoietic stem cell or bone marrow transplantation =\< 3 years of pre-registration
• Known hypersensitivity to palbociclib, letrozole, fulvestrant, goserelin (if applicable) or to any of their excipients
• Known to be pregnant and planning to continue nursing
• No tumor identified on biopsy or insufficient tumor cells to obtain ER or HER2 status
• Any of the following therapies prior to registration:
• Chemotherapy =\< 2 weeks

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

Biospecimen

Retention: SAMPLES WITH DNA

Blood, tissue, urine, stool, saliva

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Biopsy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Ciara O'Sullivan, M.B., B.Ch.

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2017
• First Posted: September 13, 2017
• Study Start: November 13, 2017
• Primary Completion: March 4, 2026
• Study Completion: March 4, 2026
• Last Updated: March 6, 2025

Record last verified: 2025-03

Locations

US (3)