Sitravatinib in Metastatic Breast Cancer

Phase 2

Terminated

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

Interventions: Drug: Sitravatinib

Registration Number: NCT04123704

Lead Sponsor: Xiang Zhang

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 3

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sitravatinib	Sitravatinib	Sitravatinib 100 mg daily

Primary Outcome Measures

Name	Time	Method
Efficacy: Progression-Free Survival at 24 Weeks (PFS24)	24 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Time to Progression (TTP)	Up to 16 months	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.
Objective Response Rate (ORR)	Up to 16 months	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.
Clinical Benefit Rate (CBR)	Up to 16 months	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.
Number of Participants With Grade 3 or Higher AEs	Up to 16 months	Adverse events will be assessed and graded per the NCI CTCAEv5.