Breast Cancer Metastatic, Breast Cancer Stage IV, Breast Neoplasms, Triple Negative Breast Cancer
Conditions
Keywords
triple negative, metastatic breast cancer, sitravatinib
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.
Interventions
DRUGSitravatinib
sitravatinib capsule
Sponsors
Mirati Therapeutics Inc.
Xiang Zhang
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sitravatinib Sitravatinib 100 mg daily
Sitravatinib: sitravatinib capsule | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Disease progression | 2 |
Baseline characteristics
| Characteristic | Sitravatinib |
|---|---|
| Age, Continuous | 53.33 years STANDARD_DEVIATION 8.62 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 1 / 3 |
Outcome results
Primary
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.
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitravatinib | Efficacy: Progression-Free Survival at 24 Weeks (PFS24) | 33.3 percentage of participants |
Secondary
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.
Time frame: Up to 16 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitravatinib | Clinical Benefit Rate (CBR) | 66.7 percentage of participants |
Secondary
Number of Participants With Grade 3 or Higher AEs
Adverse events will be assessed and graded per the NCI CTCAEv5.
Time frame: Up to 16 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sitravatinib | Number of Participants With Grade 3 or Higher AEs | 2 Participants |
Secondary
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.
Time frame: Up to 16 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitravatinib | Objective Response Rate (ORR) | 33.3 percentage of participants |
Secondary
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.
Time frame: Up to 16 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitravatinib | Time to Progression (TTP) | 24.6 weeks | Standard Deviation 16.3 |