Study of MLN4924 in Adult Patients With Nonhematologic Malignancies

July 15, 2013 updated by: Millennium Pharmaceuticals, Inc.

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

This study is an open-label, multicenter, Phase 1, dose escalation study of MLN4924 in adult patients with nonhematologic malignancies. This study will be the first to administer MLN4924 in humans. The patient population will consist of adults with any form of nonhematologic malignancy for which standard, curative, life prolonging, or palliative treatment does not exist or is no longer effective.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

62

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital
    • Texas
      • San Antonio, Texas, United States, 78229
        • Institute for Drug Development
      • San Antonio, Texas, United States, 78229
        • Cancer Therapy & Research Center at the UT Health Science Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female patients 18 years or older
  • Eastern Cooperative Oncology Group performance status 0-2
  • Patients must have a diagnosis of a nonhematologic malignancy for which standard curative, life-prolonging, or palliative treatment does not exist or is no longer effective.
  • Expected survival longer than 6 weeks from enrollment in the study
  • Radiographically or clinically evaluable tumor
  • Suitable venous access for the conduct of blood sampling for MLN4924
  • Tumor tissue that, in the opinion of the investigator, can be safely biopsied using a core needle
  • Male patients must use an appropriate method of barrier contraception
  • Female patients must be postmenopausal, surgically sterilized, or willing to use reliable methods of birth control
  • Voluntary written consent

Exclusion Criteria:

  • Pregnant or lactating
  • Major surgery within 14 days prior to the first dose of study treatment
  • Serious infection within 14 days prior to the first dose of study treatment
  • Receiving antibiotic therapy within 14 days prior to the first dose of study treatment
  • Life-threatening illness unrelated to cancer
  • Diarrhea that is greater than Grade 1 in severity
  • Systemic antineoplastic therapy within 21 days preceding first dose of study treatment
  • Radiotherapy within 21 days preceding first dose of study treatment
  • Prior treatment with radiation therapy involving ≥25% of the hematopoietically active bone marrow
  • CYP3A inducers within 14 days before the first dose of MLN4924. Moderate and strong CYP3A inhibitors and CYP3A inducers are not permitted during the study.
  • Clinically significant central nervous system metastases
  • Absolute neutrophil count <1,500/mm3; platelet count <100,000/mm3
  • Patients with a prothrombin time or aPTT > 1.5 x the upper limit of the normal range, or with a history of a coagulopathy or bleeding disorder
  • Ongoing anti-coagulant therapy that can not be held to permit tumor biopsy
  • Calculated creatinine clearance <50 mL/minute
  • Bilirubin >1.5 times the upper limit of normal; aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase >2.5 times the upper limit of normal.
  • Uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within the past 6 months
  • Abnormalities on 12-lead electrocardiogram including, but not limited to, changes in rhythm and intervals that in the opinion of the investigator are considered to be clinically significant
  • Known human immunodeficiency virus positive or hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
  • Treatment with any investigational products within 28 days preceding the first dose of study treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
MLN4924
Drug: MLN4924
IV dose escalation for 5 consecutive days followed by a rest period of 16 days for a 21 day cycle. Treated may continue until disease progression or unacceptable toxicity develops.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Determine the safety profile, MTD and PK/pharmacodynamics of MLN4924
Time Frame: Maximum duration of therapy for 12 months
Maximum duration of therapy for 12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Disease response
Time Frame: Day 21, every other cycle and end of study
Day 21, every other cycle and end of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Millennium Pharmaceuticals, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2008

Primary Completion (Actual)

February 1, 2012

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

May 9, 2008

First Submitted That Met QC Criteria

May 13, 2008

First Posted (Estimate)

May 14, 2008

Study Record Updates

Last Update Posted (Estimate)

July 16, 2013

Last Update Submitted That Met QC Criteria

July 15, 2013

Last Verified

July 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C15001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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