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Trial record 1 of 1 for:    NCT02524951
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Safety and Tolerability of MSI-1436C in Metastatic Breast Cancer

This study is currently recruiting participants.
See Contacts and Locations
Verified December 2016 by Daniel Budman, Northwell Health
Sponsor:
Collaborator:
DepYmed Inc.
Information provided by (Responsible Party):
Daniel Budman, Northwell Health
ClinicalTrials.gov Identifier:
NCT02524951
First received: August 12, 2015
Last updated: December 8, 2016
Last verified: December 2016
  Purpose
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 Intervention Phase
Metastatic Breast Cancer Drug: MSI-1436C Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Daniel Budman, Northwell Health:

Primary Outcome Measures:
  • 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:
  • 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.

  • 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.


  • 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.


  • 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.

  • Time to reach cmax [ Time Frame: one year ]
    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) [ Time Frame: one year ]
    The time required for the concentration of MSI-1436C to reach half of its original value.


Estimated Enrollment: 21
Study Start Date: April 2016
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02524951

Contacts
Contact: Xinhua Zhu, MD 516-734-8898 xzhu1@nshs.edu
Contact: Ruby Sharma, MD 516-734-8963 rsharma5@nshs.edu

Locations
United States, New York
CFAM / Monter Cancer Center Recruiting
Lake Success, New York, United States, 11042
Contact: Daniel Budman, MD    516-734-8958    dbudman@northwell.edu   
Contact    (516) 734-8896      
Principal Investigator: Daniel Budman, MD         
Sub-Investigator: Ruby Sharma, MD         
Sub-Investigator: Xinhua Zhu, MD         
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     History of Changes
Other Study ID Numbers: IIS-0039
Study First Received: August 12, 2015
Last Updated: December 8, 2016
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

ClinicalTrials.gov processed this record on July 24, 2017