Utilizing Multiomic Advanced Diagnostics to Identify CDK 4/6 Inhibitor Response Predictors and a Post-treatment Multiomic Signature for Patients With ER+/HER2- Metastatic Breast Cancer

• ClinicalTrials.gov Identifier: NCT03195192
• Recruitment Status: Completed
• First Posted: June 22, 2017
• Last Update Posted: July 1, 2020
• Sponsor: Side-Out Foundation
• Collaborator: Translational Drug Development
• Information provided by (Responsible Party): Side-Out Foundation

Tracking Information

• First Submitted Date: June 9, 2017
• First Posted Date: June 22, 2017
• Last Update Posted Date: July 1, 2020
• Actual Study Start Date: March 9, 2017
• Actual Primary Completion Date: June 30, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 19, 2017)

Evaluate baseline phosphorylated RB levels in tumor tissue as a predictive marker of response to palbociclib or ribociclib as first line treatment for ER+/HER2- metastatic breast cancer [ Time Frame: 2 years ]

Establish baseline values in tumor tissue to use as predictive markers

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 19, 2017)

• Evaluate baseline biomarkers which are direct substrates of CDK 4/6 or controlled secondarily by CDK 4/6 kinase activity as qualifying predictive markers of response to CDK 4/6 inhibitors as first line treatment for ER+/HER2- metastatic breast cancer [ Time Frame: 2 years ]
  Identify CDK 4/6 kinase which are either direct substrates or controlled secondarily by CDK 4/6 activity.
• Evaluate tumor tissue collected at time of disease progression, for post CDK 4/6 inhibitor treatment changes in biomarkers which are either direct substrates of Cyclin Dependent (CDK) 4/6 kinase or controlled secondarily by CDK 4/6 kinase activity. [ Time Frame: 2 years ]
  Evaluate tissue collected at progression for changes in CDK 4/6 biomarkers after treatment with CDK 4/6 inhibitors.
• Evaluate tumor tissue collected at time of disease progression for measurement of the activation state signaling pathways that are known markers for endocrine resistance (e.g. AKT-mTOR signaling). [ Time Frame: 2 years ]
  Evaluate tissue collected at progression for activation state of signaling pathways that are known markers for endocrine resistance
• Determine frequency when "multi-omic" profiling: proteomic and genomic profiling analysis of patient's tumor yields a target against which there is an FDA-approved agent or therapeutic regimen. [ Time Frame: 2 years ]
  Evaluate frequency with which multiomic profiling analysis of patient's tumor identifies a target that can be treated by an FDA-approved agent or regimen
• Determine percent of time multiomic profiling based treatment recommendation is different than treatment selected by the patient's physician once a patient shows progression after first line treatment with palbociclib or ribociclib [ Time Frame: 2 years ]
  Evaluate percentage of time when treatment recommendations found with multiomic profiling is different than treatment selected by a patient's physician

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: June 19, 2017)

Perform RPPA based batch analysis of all samples at the end of this study to measure 50-100 protein signaling targets. Protein activation will be correlated with clinical response. [ Time Frame: 2 years ]

The data from this exploratory analysis will help generate hypotheses for future studies.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Utilizing Multiomic Advanced Diagnostics to Identify CDK 4/6 Inhibitor Response Predictors and a Post-treatment Multiomic Signature for Patients With ER+/HER2- Metastatic Breast Cancer
• Official Title: Utilizing Multiomic Advanced Diagnostics to Identify CDK 4/6 Inhibitor Response Predictors and a Post-treatment Multiomic Signature for Patients With ER+/HER2- Metastatic Breast Cancer
• Brief Summary: This is an open-label, multicenter study in patients with metastatic breast cancer who are candidates for standard first line treatment with palbociclib or ribociclib plus endocrine therapy. To be eligible, patients must have received no prior chemotherapeutic or hormonal regimen for metastatic disease. However, patients may still be considered eligible if they have already started treatment with endocrine therapy (an aromatase inhibitor or fulvestrant) plus palbociclib or ribociclib for no longer than 4 weeks prior to study enrollment, as long as they meet all other eligibility criteria. Eligible patients must have had a diagnostic biopsy of the metastatic lesion no more than 4 months prior to study enrollment and with sufficient tissue to complete the proposed biomarker analysis. Patients who develop disease progression within the first 12 months of starting palbociclib or ribociclib plus endocrine therapy will be eligible for an optional additional tissue biopsy at time of disease progression to repeat the analysis at time of disease progression and obtain real-time (10-14-day turn-around) multi-omic data produced under College of American Pathologist (CAP)/Clinical Laboratory Improvement Amendments (CLIA) development and/or compliant practices.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description:

Open-label

Primary Purpose: Other

• Condition: Metastatic Breast Cancer

Intervention

Other: biomarker study

This is a biomarker study

Study Arms

Single arm

This is a biomarker study analyzing tissue for baseline biomarkers and collecting tissue at progression for further analysis of biomarkers changes after treatment with CDK 4/6 inhibitors and endocrine therapy

Intervention: Other: biomarker study

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 30, 2020): 28
• Original Estimated Enrollment (submitted: June 19, 2017): 100
• Actual Study Completion Date: June 30, 2020
• Actual Primary Completion Date: June 30, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients must have histologically or cytologically proven diagnosis of adenocarcinoma of the breast with evidence of locoregionally recurrent or metastatic disease.
• Tumors must be estrogen and/or progesterone receptor positive according to ASCO/CAP 2010 guidelines as either ER or PR ≥ 1% positive nuclear staining by immunohistochemistry based on local laboratory results.
• Tumors must be HER2 negative as defined according to ASCO/CAP 2013, as HER2 0 - 1+ by IHC or non-amplified FISH or CISH. If HER2 IHC is 2+, FISH/CISH must be performed and must not be positive (HER2/CEP17 ratio must be < 2, and HER2 copy number < 6 signals/cell), but otherwise FISH/CISH is not required if IHC is 0 or 1+ by institutional standards.
• Must be candidates to receive endocrine therapy and palbociclib or ribociclib as first-line treatment for their advanced disease. Patients will be considered eligible for study enrollment if they have started on treatment with a standard dose and schedule of palbociclib or ribociclib and endocrine therapy (aromatase inhibitor or fulvestrant) as long as they have not started palbociclib or ribociclib treatment for longer than 4 weeks from time of study enrollment, have sufficient tissue to perform the proposed tissue analysis and must meet all other eligibility criteria. Endocrine therapy can be initiated up to 4 weeks prior to starting palbociclib or ribociclib.
• Patients must have measurable disease by RECIST v.1.1 or bone disease as their only site of disease (with bone lesions confirmed by CT, MRI or bone X-ray).
• No prior treatment with chemotherapy for a diagnosis of locoregionally recurrent or metastatic breast cancer is allowed.
• Be ≥ 18 years of age
• Have an ECOG score of 0-1

• Postmenopausal women defined as women with:

  • Prior bilateral surgical oophorectomy, or
  • Medically confirmed post-menopausal status defined as spontaneous cessation of regular menses for at least 12 consecutive months or follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol blood levels in their respective postmenopausal ranges.
• Premenopausal women will be considered eligible for study participation if they are receiving medical ovarian suppression with luteinizing hormone-releasing hormone (LHRH) agonists with documented estradiol blood levels in their respective postmenopausal ranges.
• Archive tumor tissue (obtained from a biopsy or surgical resection of a metastatic lesion done within 4 months from study enrollment) availability is required for patient participation. If the available tissue is insufficient for the required baseline analysis, the patients are given the option to repeat the biopsy for the purpose of study participation as long as they have not already started palbociclib or ribociclib.
• Understand and provide written informed consent prior to initiation of any study-specific procedures.

Exclusion Criteria:

• Lack of archive tumor tissue from a biopsy or surgical resection of a metastatic lesion done within 4 months of study enrollment. Patients will be given an option to have a repeated biopsy of a metastatic lesion if they had a diagnostic tumor biopsy intended for use in the current study that was performed more than 4 months prior to analysis, or there is insufficient tissue from the initial biopsy to complete the analysis, as long as they have not started treatment with a CDK 4/6 inhibitor. Otherwise, the patient will be excluded from the study participation.
• Have symptomatic CNS metastasis. Patients with a history of CNS metastases who have been treated with whole brain irradiation must be stable without symptoms for 4 weeks after completion of treatment, with image documentation required, and must be either off steroids or on a stable does of steroids for ≥ 4 weeks prior to enrollment.
• Have uncontrolled concurrent illness including, but not limited to, ongoing or active serious infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmias, psychiatric illness, or situations that would limit compliance with the study requirements or ability to willingly give written informed consent.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03195192
• Other Study ID Numbers: SO-BCA-003
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Side-Out Foundation
• Original Responsible Party: Translational Drug Development
• Current Study Sponsor: Side-Out Foundation
• Original Study Sponsor: Translational Drug Development
• Collaborators: Translational Drug Development
• Investigators: Not Provided
• PRS Account: Side-Out Foundation
• Verification Date: June 2020