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, 100 mg daily, until their cancer worsens, or until they develop intolerable side effects.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

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 breast cancer (beyond curative management) that is measurable according to RECIST 1.1 criteria. Note: Patients with bone-only disease are eligible if there is at least 1 lytic lesion that can be followed for response.
• 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 archival tissue from metastatic or locally advanced breast cancer for the analysis of PTPN12 status
• At least one prior line of chemotherapy with or without a PD-L1 or PD-1 antibody in the metastatic setting
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)

• 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 ULN or ≤ 5.0 × ULN for patients with documented liver metastases.
  • Creatinine within normal institutional limits
  • Creatinine clearance ≥ 30 mL/min
  • 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 starting study treatment.
• If sexually active in a way that could lead to pregnancy, participant must agree to use a highly effective method of birth control starting at the time of informed consent and continuing throughout the study and for at least 3 months after the final dose of sitravatinib.
• Ability to understand and the willingness to give informed consent

Exclusion Criteria:

• Uncontrolled hypertension defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100, on two or more occasions within 30 days prior to enrollment.
• Imaging suggestive of Lymphangitic carcinomatosis in the lung, or use of home oxygen
• Untreated brain metastases.
• Women who are pregnant or nursing
• Concurrent metastatic disease of another tumor type
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of sitravatinib
• History of stroke, pulmonary embolus (PE), or myocardial infarction (MI)
• Known proteinuria of ≥ 2 g urinary protein/24 h
• HIV-positive participants
• History of Hepatitis C or Hepatitis B infection
• History of congestive heart failure (CHF), and/or LVEF less than 50%
• Concurrent use of medications that prolong QTc (listed in Section 9, Table 11). These medications need to be discontinued at least 2 weeks prior to starting study treatment.
• Concurrent medical condition that, in the sole judgment of the principal investigator, would make the patient inappropriate for trial participation.

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 100 mg daily	Drug: Sitravatinib; sitravatinib capsule; Other Names: MGCD516

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy: Progression-Free Survival at 24 Weeks (PFS24)	Progression-free survival 24 weeks after starting study treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Progressive Disease, >=20% increase in the sum of the smallest diameter of target lesions, or appearance of one or more new lesions.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Progression (TTP)	Time to progression is defined as the duration of time from initiation of study treatment until progression. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Progressive Disease, >=20% increase in the sum of the smallest diameter of target lesions, or appearance of one or more new lesions.	Up to 16 months
Objective Response Rate (ORR)	Objective response rate is defined as the percentage of participants who achieve a Complete Response (CR) or Partial Response (PR) to treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	Up to 16 months
Clinical Benefit Rate (CBR)	Clinical benefit rate is defined as the percentage of participants who achieve Complete Response (CR), Partial Response (PR), or Stable Disease (SD). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither >=30% decrease in sum of longest diameter of target lesions nor >=20% increase in sum of shortest diameter of target lesions.	Up to 16 months
Number of Participants With Grade 3 or Higher AEs	Adverse events will be assessed and graded per the NCI CTCAEv5.	Up to 16 months

Collaborators and Investigators

• Sponsor: Xiang Zhang
• 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): January 22, 2023
• Study Completion (Actual): January 22, 2023

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): August 26, 2024
• Last Update Submitted That Met QC Criteria: July 31, 2024
• Last Verified: June 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