Sitravatinib in Metastatic Breast Cancer

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Breast Neoplasms; Triple Negative Breast Cancer; Breast Cancer Stage IV; Breast Cancer Metastatic
• Intervention / Treatment: Drug: Sitravatinib

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Anne Pavlick, BS; Phone Number: 713-798-7814; Email: clinical-research@breastcenter.tmc.edu

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sitravatinib; Sitravatinib 120 mg daily	Drug: Sitravatinib; sitravatinib capsule; Other Names: MGCD516

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: C. Kent Osborne, MD
• Collaborators: Mirati Therapeutics Inc.
• Investigators: Principal Investigator: C. Kent Osborne, MD, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2021
• Primary Completion (Actual): September 22, 2021
• Study Completion (Actual): September 22, 2021

Study Registration Dates

• First Submitted: October 9, 2019
• First Submitted That Met QC Criteria: October 9, 2019
• First Posted (Actual): October 11, 2019

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: triple negative; metastatic breast cancer; sitravatinib
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms
• Other Study ID Numbers: H-43432

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No