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

NCT02524951 | Terminated Phase 1 DMC

• 1 other identifier: IIS-0039
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Area under the plasma concentration versus time curve (AUC)

  one year

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  one year

• response rates

  one year

• Peak plasma concentration of the drug after administration (cmax)

  one year

• Time to reach cmax

  one year

Study Arms (7)

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

Interventions

MSI-1436C DRUG

Dose escalation, single intravenous infusion twice a week for 3 weeks on a 4-week cycle.

Also known as: Trodusquemine

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

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Northwell Health: lead
• DepYmed Inc.: collaborator

Study Sites (1)

CFAM / Monter Cancer Center

Lake Success, New York, 11042, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

3-N-1(spermine)-7, 24-dihydroxy-5-cholestane 24-sulfate

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Daniel Budman, MD

  North Shore LIJ Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director Translational Research, Cancer Institute

Study Record Dates

• First Submitted: August 12, 2015
• First Posted: August 17, 2015
• Study Start: April 1, 2016
• Primary Completion: July 1, 2017
• Study Completion: May 14, 2018
• Last Updated: May 18, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)