Safety and Tolerability of MSI-1436C in Metastatic Breast Cancer
- Registration Number
- NCT02524951
- Lead Sponsor
- Northwell Health
- Brief Summary
This is a Phase I, open-label, dose escalation study. MSI-1436 will be administered as a single intravenous infusion twice a week for 3 weeks on a 4-week cycle.
- Detailed Description
This is a Phase I, open-label, dose escalation study. MSI-1436 will be administered as a single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will be enrolled according to a standard Phase I Fibonacci design to receive MSI-1436. Drug infusions will last approximately 2 hours. If a subject has a dose-limiting toxicity (DLT) at any time during the study, MSI-1436 will be held and either re-started or discontinued in that subject as per the Dose Adjustments and Toxicities Guidelines.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Female
- Target Recruitment
- 5
- Signed, witnessed, and dated Institutional Review Board (IRB) approved Informed Consent Form (ICF).
- Pathologically confirmed metastatic breast cancer with measurable disease. Metastatic sites must be measurable on CT, MRI, or FDG-PET/CT as per the revised RECIST v1.1 criteria or measurable disease on physical examination.
A metastatic site must be biopsy proven
- Life expectancy ≥3 months.
- Patients enrolled must have received 2 or more lines of therapy and all patients with HER2 expressing tumors must have received HER2 targeted therapy.
- Female Age ≥18 years.
- Stable brain metastasis is permitted. This is not considered measurable disease.
Stable brain metastasis is defined as no change on CT scan or MRI for minimum of 2 months AND no change in steroid dose for a minimum of 4 weeks
- A negative serum pregnancy test, if female of reproductive potential. Reproductive potential defined as age < 55 or with no menses for < 1 year
- Screening laboratory values as follows:
Total bilirubin ≤1.5 times upper limit of normal (ULN). Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine aminotransferase (serum glutamic pyruvate transaminase)≤ 2.5 times ULN.
Serum creatinine ≤2.0 mg/dL or calculated creatinine clearance ≥60 mL/min. Absolute neutrophil count >1,500 cells/mm3. Platelet count ≥100,000 plt/mm3. Hemoglobin ≥ 8 g/dL. Non-diabetic
- Pregnant or breast-feeding
- ECOG Performance Status greater than 2
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description MSI-1436C (Trodusquemine) 26 mg/m2 IV MSI-1436C Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 26 mg/m2. Drug infusions will last approximately 2 hours. MSI-1436C (Trodusquemine) 34 mg/m2 IV MSI-1436C Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 34 mg/m2 . Drug infusions will last approximately 2 hours. MSI-1436C (Trodusquemine) 96 mg/m2 IV MSI-1436C Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 96 mg/m2 . Drug infusions will last approximately 2 hours. MSI-1436C (Trodusquemine) 74 mg/m2 IV MSI-1436C Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 74 mg/m2 . Drug infusions will last approximately 2 hours. MSI-1436C (Trodusquemine) 57 mg/m2 IV MSI-1436C Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 57 mg/m2. Drug infusions will last approximately 2 hours. MSI-1436C (Trodusquemine) 20 mg/m2 IV MSI-1436C Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 20 mg/m2. Drug infusions will last approximately 2 hours. MSI-1436C (Trodusquemine) 44 mg/m2 IV MSI-1436C Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 44 mg/m2 . Drug infusions will last approximately 2 hours.
- Primary Outcome Measures
Name Time Method Maximally Tolerated Dose (MTD) of MSI-1436 one year Subjects will be enrolled according to a standard Phase I Fibonacci design to receive MSI-1436C. If a subject has a dose-limiting toxicity (DLT) at any time during the study, MSI-1436C will be held and either re-started or discontinued in that subject as per the Dose Adjustments and Toxicities Guidelines.
- Secondary Outcome Measures
Name Time Method Peak plasma concentration of the drug after administration (cmax) one year The maximum (or peak) serum concentration that MSI-1436C achieves in the plasma after the drug has been administrated and prior to the administration of a second dose.
Area under the plasma concentration versus time curve (AUC) one year The area under the plasma drug concentration-time curve (AUC) reflects the actual body exposure to drug after administration of a dose of MSI-1436C.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 one year All adverse events and dose-limiting toxicities will be recorded and tabulated. A dose-limiting toxicity (DLT) will be defined as any grade 3 or higher NCI Common Toxicity Criteria adverse event (CTCAE) that is deemed related to the study drug MSI-1436C, any infusion reaction necessitating drug discontinuation, or any other drug related adverse event leading to the study drug discontinuation.
Descriptive statistics will be used to summarize adverse events and dose-limiting toxicities. The proportion of AEs and DLTs will be calculated along with their corresponding exact 95% confidence intervals.Time required for the concentration of MSI-1436C to reach half of its original value, or half life (t1/2) one year The time required for the concentration of MSI-1436C to reach half of its original value.
Time to reach cmax one year The amount of time for MSI-1436C to reach Cmax
response rates one year To assess the response rates of MSI-1436C in metastatic breast cancer patients the outcome variable of interest is time-to-progression. Patients who have not progressed (or who have not died) as of their last known follow-up, will be considered 'censored' for the time-to-progression analysis.
Time-to-progression will be estimated using the Kaplan-Meier Product-Limit Method. Any post- hoc group comparisons will be carried out using the log-rank test. Patients who have not progressed (or who have not died) as of their last known follow-up, will be considered 'censored' for the time-to-progression analysis.
Trial Locations
- Locations (1)
CFAM / Monter Cancer Center
🇺🇸Lake Success, New York, United States