Sitravatinib in Metastatic Breast Cancer

Study Overview
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Brief Summary
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This study evaluates the efficacy of sitravatinib in patients with metastatic breast cancer. All study participants will receive sitravatinib, 120 mg daily, until their cancer worsens, or until they develop intolerable side effects.

Official Title
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A Phase II Study of Sitravatinib in Metastatic, Pre-treated, Triple Negative Breast Cancer

Conditions
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Breast Neoplasms, Breast Cancer Stage IV, Triple Negative Breast Cancer, Breast Cancer Metastatic

Intervention / Treatment
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* Drug: Sitravatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women or men age 18 and older Metastatic or locally advanced inoperable disease breast cancer Tumor is estrogen receptor (ER) negative and progesterone receptor (PR) negative per the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) Guidelines of 2010. Tumor is HER2neu negative per ASCO/CAP Guidelines of 2018 Patient has tumor tissue blocks from metastatic or locally advanced breast cancer (beyond curative management) for the analysis of PTPN12 status Metastatic disease or locally advanced breast cancer (beyond curative management) that is measurable according to RECIST 1.1 criteria. Patients with bone only disease are eligible for enrollment if there is at least one lytic lesion that can be followed for response. At least one prior line of chemotherapy with or without a PDL1 or PD1 antibody in metastatic setting Patient has Eastern Cooperative Oncology Group (ECOG) performance status <2 (Karnofsky > 60%) Patients must have normal organ and marrow function as defined below: Absolute neutrophil count > 1000/mcL Hemoglobin > 11 g/dL Platelets >100,000/mcL Total bilirubin < 1.5 X normal institutional limits Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) < 2.5 X institutional upper limit of normal (ULN) or ≤ 5.0 × ULN for patients with documented liver metastases. Creatinine within normal institutional limits Creatinine clearance > 30 mL/min/1.73 m2 Normal left ventricular ejection (LVEF) function defined as normal left ventricular wall motion and ejection fraction of ≥ 50%. If patient has brain metastasis, documented treatment and stability for at least 30 days by scans and off steroids at the time of enrollment Women of child bearing age and actively menstruating must have a negative pregnancy test prior to study enrollment. Ability to understand and the willingness to give informed consent Exclusion Criteria: Untreated hypertension defined as systolic blood pressure > 140 and/or diastolic blood pressure > 90 on two or more occasions within the past 30 days previous to enrollment Imaging suggestive of Lymphangitic carcinomatosis in the lung, or use of home oxygen Untreated brain metastases. Pregnancy or lactation at time of trial enrollment Concomitant metastatic disease of another tumor type Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs History of stroke, pulmonary embolus (PE), or myocardial infarction (MI) at any time Known Proteinuria of ≥ 2 g/24 h HIV-positive participants. History of Hepatitis C and Hepatitis B infection Documented history of congestive heart failure, and/or LVEF less than 50% Concurrent use of medications on the prohibited medications list, unless these medications can be replaced by alternatives. These medications need to be discontinued at least 2 weeks prior to enrollment. Presence of other medical condition that, in the sole judgment of the principal investigator, makes the patient not a good candidate.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sitravatinib<br>Sitravatinib 120 mg daily | Drug: Sitravatinib<br>* sitravatinib capsule<br>* Other names: MGCD516;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Benefit Rate | Clinical Benefit Rate is defined as Objective Response Rate (ORR) plus Stable Disease (SD) for 24 weeks as per Response Evaluation Criteria In Solid Tumours (RECIST) v1.1. ORR is defined Complete Response plus Partial Response per RECIST v1.1 criteria. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression | Time to progression is calculated from Day 1 of sitravatinib therapy to first evidence of disease progression, as determine by Response Evaluation Criteria in Solid Tumors (RECIST). | Up to 5 years | 
| Number of patients with Grade 3 or higher adverse events | Adverse events will be assessed and graded according to the National Cancer Institute Common Terminology Criteria version 5.0. | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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triple negative, metastatic breast cancer, sitravatinib