Safety and Tolerability of MSI-1436C in Metastatic Breast Cancer

A Phase I Study of the Safety and Tolerability of Single Agent MSI-1436C in Metastatic Breast Cancer Patients

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.

Study Overview

• Status: Terminated
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: MSI-1436C

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Lake Success, New York, United States, 11042
      • CFAM / Monter Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• Pregnant or breast-feeding
• ECOG Performance Status greater than 2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MSI-1436C (Trodusquemine) 20 mg/m2 IV; 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.	Drug: MSI-1436C; Dose escalation, single intravenous infusion twice a week for 3 weeks on a 4-week cycle.; Other Names: Trodusquemine
Experimental: MSI-1436C (Trodusquemine) 26 mg/m2 IV; 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.	Drug: MSI-1436C; Dose escalation, single intravenous infusion twice a week for 3 weeks on a 4-week cycle.; Other Names: Trodusquemine
Experimental: MSI-1436C (Trodusquemine) 34 mg/m2 IV; 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.	Drug: MSI-1436C; Dose escalation, single intravenous infusion twice a week for 3 weeks on a 4-week cycle.; Other Names: Trodusquemine
Experimental: MSI-1436C (Trodusquemine) 44 mg/m2 IV; 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.	Drug: MSI-1436C; Dose escalation, single intravenous infusion twice a week for 3 weeks on a 4-week cycle.; Other Names: Trodusquemine
Experimental: MSI-1436C (Trodusquemine) 57 mg/m2 IV; 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.	Drug: MSI-1436C; Dose escalation, single intravenous infusion twice a week for 3 weeks on a 4-week cycle.; Other Names: Trodusquemine
Experimental: MSI-1436C (Trodusquemine) 74 mg/m2 IV; 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.	Drug: MSI-1436C; Dose escalation, single intravenous infusion twice a week for 3 weeks on a 4-week cycle.; Other Names: Trodusquemine
Experimental: MSI-1436C (Trodusquemine) 96 mg/m2 IV; 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.	Drug: MSI-1436C; Dose escalation, single intravenous infusion twice a week for 3 weeks on a 4-week cycle.; Other Names: Trodusquemine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximally Tolerated Dose (MTD) of MSI-1436	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.	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration versus time curve (AUC)	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.	one year
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	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.	one year
response rates	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.	one year
Peak plasma concentration of the drug after administration (cmax)	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.	one year
Time to reach cmax	The amount of time for MSI-1436C to reach Cmax	one year
Time required for the concentration of MSI-1436C to reach half of its original value, or half life (t1/2)	The time required for the concentration of MSI-1436C to reach half of its original value.	one year

Collaborators and Investigators

• Sponsor: Northwell Health
• Collaborators: DepYmed Inc.
• Investigators: Principal Investigator: Daniel Budman, MD, North Shore LIJ Cancer Institute

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): May 14, 2018

Study Registration Dates

• First Submitted: August 12, 2015
• First Submitted That Met QC Criteria: August 13, 2015
• First Posted (Estimate): August 17, 2015

Study Record Updates

• Last Update Posted (Actual): May 18, 2018
• Last Update Submitted That Met QC Criteria: May 15, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: IIS-0039

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No