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

Metastatic Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02524951
• Other study ID #: IIS-0039
• Status: Terminated
• Phase: Phase 1
• Start date: April 2016
• Est. completion date: May 14, 2018

Study information

• Verified date: May 2018
• Source: Northwell Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: May 14, 2018
• Est. primary completion date: July 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• MSI-1436C
Dose escalation, single intravenous infusion twice a week for 3 weeks on a 4-week cycle.

Locations

Country	Name	City	State
United States	CFAM / Monter Cancer Center	Lake Success	New York

Sponsors (2)

Lead Sponsor	Collaborator
Northwell Health	DepYmed Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Time to reach cmax	The amount of time for MSI-1436C to reach Cmax	one year
Secondary	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