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

NCT ID: NCT05244434

Last Updated: 2022-06-09

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-03
• Study Completion Date: 2023-01-26

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.

Detailed Description

PRIMARY OBJECTIVE:

I. To identify predictive immune biomarkers and mechanisms of response to ribociclib or palbociclib in advanced, hormone receptor positive breast cancer patients.

SECONDARY OBJECTIVES:

I. Identify changes in antigen presentation machinery and costimulatory molecules on circulating myeloid cells as a result of ribociclib or palbociclib treatment.

II. Characterize the dynamic remodeling of circulating myeloid cell composition that occur as a result of ribociclib or palbociclib treatment.

III. Characterize acquired immune tumor microenvironment features of resistance in patients that progress while undergoing ribociclib or palbociclib treatment.

EXPLORATORY OBJECTIVE:

I. To study the association between immune biomarkers and clinical response.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

PROSPECTIVE COHORT: Patients receive standard of care (SOC) treatment consisting of ribociclib or palbociclib plus aromatase inhibitor (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.

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

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Prospective cohort (SOC treatment, biopsy, blood collection)

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.

Group Type: EXPERIMENTAL

Best Practice

Intervention Type: OTHER

Given standard of care ribociclib + AI or palbociclib + AI

Biopsy

Intervention Type: PROCEDURE

Undergo biopsy of tumor tissue

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood sample collection

Laboratory Biomarker Analysis

Intervention Type: OTHER

Undergo analysis of previously collected tumor tissue

Retrospective cohort

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

Group Type: EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type: OTHER

Undergo analysis of previously collected tumor tissue

Interventions

Best Practice

Given standard of care ribociclib + AI or palbociclib + AI

Intervention Type: OTHER

Biopsy

Undergo biopsy of tumor tissue

Intervention Type: PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type: PROCEDURE

Laboratory Biomarker Analysis

Undergo analysis of previously collected tumor tissue

Intervention Type: OTHER

Other Intervention Names

standard of care; standard therapy; BIOPSY_TYPE; Bx; Biological Sample Collection; Biospecimen Collected

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• Patient is currently receiving or has received systemic corticosteroids =< 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment

• The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yuan Yuan

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Other Identifiers

NCI-2022-00238

Identifier Type: REGISTRY

Identifier Source: secondary_id

21623

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

21623

Identifier Type: -

Identifier Source: org_study_id