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

• ClinicalTrials.gov Identifier: NCT02524951
• Recruitment Status: Terminated
• First Posted: August 17, 2015
• Last Update Posted: May 18, 2018
• Sponsor: Northwell Health
• Collaborator: DepYmed Inc.
• Information provided by (Responsible Party): Daniel Budman, Northwell Health

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Metastatic Breast Cancer	Drug: MSI-1436C	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 5 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Study of the Safety and Tolerability of Single Agent MSI-1436C in Metastatic Breast Cancer Patients
• Study Start Date: April 2016
• Actual Primary Completion Date: July 2017
• Actual Study Completion Date: May 14, 2018

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Trodusquemine

Outcome Measures

Primary Outcome Measures :

1. Maximally Tolerated Dose (MTD) of MSI-1436 [ Time Frame: 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 :

1. Area under the plasma concentration versus time curve (AUC) [ Time Frame: 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.
2. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 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.

3. response rates [ Time Frame: 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.

4. Peak plasma concentration of the drug after administration (cmax) [ Time Frame: 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.
5. Time to reach cmax [ Time Frame: one year ]
   The amount of time for MSI-1436C to reach Cmax
6. Time required for the concentration of MSI-1436C to reach half of its original value, or half life (t1/2) [ Time Frame: one year ]
   The time required for the concentration of MSI-1436C to reach half of its original value.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, New York

CFAM / Monter Cancer Center

Lake Success, New York, United States, 11042

Sponsors and Collaborators

Northwell Health

DepYmed Inc.

Investigators

• Principal Investigator: Daniel Budman, MD; North Shore LIJ Cancer Institute

More Information

• Responsible Party: Daniel Budman, Director Translational Research, Cancer Institute, Northwell Health
• ClinicalTrials.gov Identifier: NCT02524951
• Other Study ID Numbers: IIS-0039
• First Posted: August 17, 2015
• Last Update Posted: May 18, 2018
• Last Verified: May 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases