Dose Escalation Study of MLN4924 in Adults With Melanoma - Full Text View

Purpose

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.

Condition	Intervention	Phase
Metastatic Melanoma	Drug: MLN4924	Phase 1

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I, Open-Label, Dose Escalation Study of MLN4924, a Novel Inhibitor of Nedd8-Activating Enzyme, in Adult Patients With Melanoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma

U.S. FDA Resources

Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures:

Maximum Tolerated Dose (MTD) and inform recommended phase 2 dose of MLN4924 [ Time Frame: Up to 12 months of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Anti-tumor activities of MLN4924 [ Time Frame: Up to 12 months of treatment ] [ Designated as safety issue: No ]
Pharmacodynamic effects of MLN4924 on blood and tumor cells [ Time Frame: Primarily assessed during the first cycle of therapy ] [ Designated as safety issue: No ]

Enrollment:	37
Study Start Date:	December 2009
Study Completion Date:	January 2013
Primary Completion Date:	May 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: MLN4924 MLN4924 via IV infusion	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)

Arms

Assigned Interventions

Experimental: MLN4924

MLN4924 via IV infusion

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)

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01011530

Locations

United States, California
The Angeles Clinic and Research Institute
Santa Monica, California, United States, 90404

Sponsors and Collaborators

Millennium Pharmaceuticals, Inc.

Investigators

Study Director:

Medical Monitor

Millennium Pharmaceuticals, Inc.

More Information

No publications provided

Responsible Party:	Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT01011530 History of Changes
Other Study ID Numbers:	C15005
Study First Received:	November 9, 2009
Last Updated:	February 27, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Millennium Pharmaceuticals, Inc.:

Melanoma

Additional relevant MeSH terms:

Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on May 23, 2013