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

Primary Purpose

Metastatic Breast Cancer

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
MSI-1436C
Sponsored by
Northwell Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • CFAM / Monter Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

MSI-1436C (Trodusquemine) 20 mg/m2 IV

MSI-1436C (Trodusquemine) 26 mg/m2 IV

MSI-1436C (Trodusquemine) 34 mg/m2 IV

MSI-1436C (Trodusquemine) 44 mg/m2 IV

MSI-1436C (Trodusquemine) 57 mg/m2 IV

MSI-1436C (Trodusquemine) 74 mg/m2 IV

MSI-1436C (Trodusquemine) 96 mg/m2 IV

Arm Description

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.

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
Time to reach cmax
The amount of time for MSI-1436C to reach Cmax
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.

Full Information

First Posted
August 12, 2015
Last Updated
May 15, 2018
Sponsor
Northwell Health
Collaborators
DepYmed Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02524951
Brief Title
Safety and Tolerability of MSI-1436C in Metastatic Breast Cancer
Official Title
A Phase I Study of the Safety and Tolerability of Single Agent MSI-1436C in Metastatic Breast Cancer Patients
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Terminated
Why Stopped
lack of interest by sponsor
Study Start Date
April 2016 (undefined)
Primary Completion Date
July 2017 (Actual)
Study Completion Date
May 14, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Northwell Health
Collaborators
DepYmed Inc.

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MSI-1436C (Trodusquemine) 20 mg/m2 IV
Arm Type
Experimental
Arm Description
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.
Arm Title
MSI-1436C (Trodusquemine) 26 mg/m2 IV
Arm Type
Experimental
Arm Description
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.
Arm Title
MSI-1436C (Trodusquemine) 34 mg/m2 IV
Arm Type
Experimental
Arm Description
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.
Arm Title
MSI-1436C (Trodusquemine) 44 mg/m2 IV
Arm Type
Experimental
Arm Description
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.
Arm Title
MSI-1436C (Trodusquemine) 57 mg/m2 IV
Arm Type
Experimental
Arm Description
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.
Arm Title
MSI-1436C (Trodusquemine) 74 mg/m2 IV
Arm Type
Experimental
Arm Description
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.
Arm Title
MSI-1436C (Trodusquemine) 96 mg/m2 IV
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
MSI-1436C
Other Intervention Name(s)
Trodusquemine
Intervention Description
Dose escalation, single intravenous infusion twice a week for 3 weeks on a 4-week cycle.
Primary Outcome Measure Information:
Title
Maximally Tolerated Dose (MTD) of MSI-1436
Description
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.
Time Frame
one year
Secondary Outcome Measure Information:
Title
Area under the plasma concentration versus time curve (AUC)
Description
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.
Time Frame
one year
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
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 Frame
one year
Title
response rates
Description
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.
Time Frame
one year
Title
Peak plasma concentration of the drug after administration (cmax)
Description
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.
Time Frame
one year
Title
Time to reach cmax
Description
The amount of time for MSI-1436C to reach Cmax
Time Frame
one year
Title
Time required for the concentration of MSI-1436C to reach half of its original value, or half life (t1/2)
Description
The time required for the concentration of MSI-1436C to reach half of its original value.
Time Frame
one year

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel Budman, MD
Organizational Affiliation
North Shore LIJ Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
CFAM / Monter Cancer Center
City
Lake Success
State/Province
New York
ZIP/Postal Code
11042
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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