Clinical trial NCT05244434: Effects of Ribociclib and Palbociclib on Tumor and Blood Characteristics in Patients With Metastatic Breast Cancer
Official title: Comparative Effects of Ribociclib and Palbociclib on Circulating and Tumor Infiltrating Myeloid Cells in Metastatic Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
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
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2022-02-17
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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)

Primary outcomes:
measure: Immune cell frequency (relative abundance, cells per parental cell)
timeFrame: 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:
measure: Single-cell gene expression
timeFrame: 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
measure: Psuedotime gene trajectory
timeFrame: 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
measure: Cells per mm^2 tissue
timeFrame: 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
measure: Cells per mm^2 cancer island
timeFrame: 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
measure: Average cell-cell distances (within neighborhood)
timeFrame: 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
measure: Cells per mm^2 stroma
timeFrame: 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
measure: Number of core cells with cell(s) in neighborhood
timeFrame: 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
measure: Number of spatial clusters
timeFrame: 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
Other outcomes:
Locations:
Study officials:
affiliation: City of Hope Medical Center
name: Yuan Yuan
role: PRINCIPAL_INVESTIGATOR
References: