NCT01011530

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
37

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Dec 2009

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 9, 2009

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 11, 2009

Completed
20 days until next milestone

Study Start

First participant enrolled

December 1, 2009

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2012

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2013

Completed
Last Updated

July 16, 2013

Status Verified

July 1, 2013

Enrollment Period

2.4 years

First QC Date

November 9, 2009

Last Update Submit

July 15, 2013

Conditions

Metastatic Melanoma

Keywords

Melanoma

Outcome Measures

Primary Outcomes (1)

  • Maximum Tolerated Dose (MTD) and inform recommended phase 2 dose of MLN4924

    Up to 12 months of treatment

Secondary Outcomes (2)

  • Anti-tumor activities of MLN4924

    Up to 12 months of treatment

  • Pharmacodynamic effects of MLN4924 on blood and tumor cells

    Primarily assessed during the first cycle of therapy

Study Arms (1)

MLN4924

EXPERIMENTAL

MLN4924 via IV infusion

Drug: MLN4924

Interventions

MLN4924DRUG

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)

MLN4924

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The Angeles Clinic and Research Institute

Santa Monica, California, 90404, United States

Location

Related Publications (1)

  • Faessel HM, Mould DR, Zhou X, Faller DV, Sedarati F, Venkatakrishnan K. Population pharmacokinetics of pevonedistat alone or in combination with standard of care in patients with solid tumours or haematological malignancies. Br J Clin Pharmacol. 2019 Nov;85(11):2568-2579. doi: 10.1111/bcp.14078. Epub 2019 Sep 4.

    PMID: 31355467DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

pevonedistat

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsNeoplasms by SiteSkin DiseasesSkin and Connective Tissue Diseases

Study Officials

  • Medical Monitor

    Millennium Pharmaceuticals, Inc.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 9, 2009

First Posted

November 11, 2009

Study Start

December 1, 2009

Primary Completion

May 1, 2012

Study Completion

January 1, 2013

Last Updated

July 16, 2013

Record last verified: 2013-07

Locations

US(1)