Dose Escalation Study of MLN4924 in Adults With Melanoma

Metastatic Melanoma Clinical Trial

Official title:

A Phase I, Open-Label, Dose Escalation Study of MLN4924, a Novel Inhibitor of Nedd8-Activating Enzyme, in Adult Patients With Melanoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01011530
• Other study ID #: C15005
• Status: Completed
• Phase: Phase 1
• First received: November 9, 2009
• Last updated: July 15, 2013
• Start date: December 2009
• Est. completion date: January 2013

Study information

• Verified date: July 2013
• Source: Millennium Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is an open-label, multicenter, phase 1, dose escalation study that will evaluate the safety profile, establish Maximum Tolerated Dose (MTD), and inform the recommended phase 2 dose of MLN4924 as well as evaluate antitumor activity in patients with metastatic melanoma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: January 2013
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Each patient must meet all of the following criteria to be enrolled in the study:

• Diagnosis of metastatic melanoma

• Measurable disease

• Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse

• Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse

• Willing and able to give written informed consent

• Suitable venous access for study-required blood sampling

• Appropriate functional status, including the recovery from the effects of prior antineoplastic therapy, and acceptable organ function as described in the protocol

Exclusion Criteria:

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

• Major surgery or, serious infections, or infections that required systematic antibiotic therapy within 14 days before the first dose of study drug

• Systemic antineoplastic or radiation therapy within 14 days or treatment with any investigational products within 21 days before the first dose of study treatment

• CYP3A inducers within 14 days of study treatment. Moderate and strong CYP3A inhibitors and CYP3A inducers are not permitted during the study

• No prior history of amiodarone in the 6 months before the first dose of MLN4924

• Diarrhea that is greater than Grade 1 as outlined in the protocol

• Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within the past 6 months

• Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection.

• Serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol

• Other clinical and laboratory assessments that do not meet the criteria specified in the protocol

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Metastatic Melanoma

Intervention

Drug:
• MLN4924
Patients will be administered MLN4924 via an IV infusion. Each 21-day treatment cycle is composed of 2 weeks intermittent dosing of MLN4924 on Days 1, 4, 8 and 11, followed by a rest period of 10 days. A cohort of patients will receive a reduced first dose on Day 1, approximately half the strength of the dose received on Days 4, 8, 11 and dose will not be administered on Day 4 if the Day 1 dose is not tolerated.(Schedule A ramp-up), or continuous weekly dosing (Days 1, 8, and 15) of MLN4924 (Schedule B)

Locations

Country	Name	City	State
United States	The Angeles Clinic and Research Institute	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD) and inform recommended phase 2 dose of MLN4924		Up to 12 months of treatment	Yes
Secondary	Anti-tumor activities of MLN4924		Up to 12 months of treatment	No
Secondary	Pharmacodynamic effects of MLN4924 on blood and tumor cells		Primarily assessed during the first cycle of therapy	No