Effects of Ribociclib and Palbociclib on Tumor and Blood Characteristics in Patients With Metastatic Breast Cancer

NCT05244434 | Withdrawn DMC

• 3 other identifiers: 21623NCI-2022-00238P30CA033572
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This clinical trial attempts to understand the differences between two chemotherapy drugs, ribociclib and palbociclib, and how they fight cancer. This study looks at tissue and blood characteristics of patients receiving these therapies in the hopes to develop a way to predict which medication would provide the most benefit to an individual patient.

Conditions

Advanced Breast Adenocarcinoma; Advanced HER2-Negative Breast Carcinoma; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; Hormone Receptor-Positive Breast Carcinoma; Metastatic Breast Adenocarcinoma; Metastatic HER2-Negative Breast Carcinoma; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8; Prognostic Stage IV Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Immune cell frequency (relative abundance, cells per parental cell)

  Will be assessed by high dimensional flow cytometry. One-way analysis of variance (ANOVAs) and non-parametric Kruskal-Wallis tests will be used to compare relative abundances across patient groups and over the course of therapy. Wilcoxon rank-sum test will be used to examine the association between each biomarker of each sample collection and pathological response as appropriate. Odds ratios and 95% conference intervals will be calculated to measure strength of associations. P-values \< 0.05 will be considered statistically significant. No adjustment for multiple comparisons will be used in view of the exploratory nature of this analysis.

  From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years

Secondary Outcomes (8)

• Single-cell gene expression

  From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years

• Psuedotime gene trajectory

  From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years

• Cells per mm^2 tissue

  From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years

• Cells per mm^2 cancer island

  From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years

• Average cell-cell distances (within neighborhood)

  From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years

Study Arms (2)

Prospective cohort (SOC treatment, biopsy, blood collection)

EXPERIMENTAL

Patients receive SOC treatment consisting of ribociclib or palbociclib plus AI. Patients undergo biopsy of tumor tissue at baseline and post-treatment. Patients also undergo collection of blood samples at baseline, on day 1 of SOC treatment cycles 2, 4, and 6, every 6 cycles thereafter, and at post-treatment.

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

Retrospective cohort

EXPERIMENTAL

Patients' tumor tissue collected during previous SOC treatment (ribociclib or palbociclib plus AI) is used for analysis.

Other: Laboratory Biomarker Analysis

Interventions

Best Practice OTHER

Given standard of care ribociclib + AI or palbociclib + AI

Also known as: standard of care, standard therapy

Prospective cohort (SOC treatment, biopsy, blood collection)

Biopsy PROCEDURE

Undergo biopsy of tumor tissue

Also known as: BIOPSY_TYPE, Bx

Prospective cohort (SOC treatment, biopsy, blood collection)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected

Prospective cohort (SOC treatment, biopsy, blood collection)

Laboratory Biomarker Analysis OTHER

Undergo analysis of previously collected tumor tissue

Prospective cohort (SOC treatment, biopsy, blood collection); Retrospective cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histological confirmed breast adenocarcinoma who meet the following criteria:
• Age: \>= 18 years and are post-menopausal
• Estrogen receptor positive (ER+) and human epidermal growth factor receptor 2 (HER2) negative breast cancer patients who prospectively may undergo evaluation for Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), ribociclib or palbociclib, as part of first-line therapy. Retrospective cohorts will be built to include either ribociclib or palbociclib treated patients with known clinical outcome
• During routine standard of care procedure, tumor that is accessible for ultrasound guided biopsy (from breast, lymph node, subcutaneous tumor, or selected liver metastasis per treating physician's discretion) or skin punch biopsy (for dermal metastasis) will be collected
• Available tumor tissue or planning on biopsy prior to initiation of CDK4/6i treatment
• Available tumor tissue or planning on biopsy at time of progression, prior to initiating subsequent therapy
• Willing to provide consent for extra tissue and blood samples

You may not qualify if:

• Patient received prior treatment with any CDK4/6 inhibitor
• Prior treatment with any chemotherapy for metastatic disease
• Patient is cognitively impaired
• Lung or bone metastasis only (not accessible by ultrasound guided biopsy)
• Patients with central nervous system (CNS) involvement unless they meet ALL the following criteria:
• Untreated brain metastases (e.g., lesions \< 1cm) not needing immediate local therapy
• Previously treated brain metastases not needing immediate local therapy
• At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment
• Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases
• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following:
• Patient is currently receiving any of the following medications and cannot be discontinued 7 days prior to starting study drug:
• Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pummelos, star-fruit, and Seville oranges
• That have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5
• Herbal preparations/medications, dietary supplements
• Warfarin or other coumadin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), newer anticoagulation agents such as direct factor Xa inhibitors, or fondaparinux is allowed

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Interventions

Practice Guidelines as Topic; Standard of Care; Biopsy

Intervention Hierarchy (Ancestors)

Guidelines as Topic; Quality Assurance, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality Indicators, Health Care; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Yuan Yuan

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2022
• First Posted: February 17, 2022
• Study Start: July 3, 2022
• Primary Completion: January 26, 2023
• Study Completion: January 26, 2023
• Last Updated: June 9, 2022

Record last verified: 2022-06