Study of MLN4924 in Adult Patients With Nonhematologic Malignancies

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00677170
First received: May 9, 2008
Last updated: July 15, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Advanced Nonhematologic Malignancies
Drug: MLN4924
Phase 1

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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Determine the safety profile, MTD and PK/pharmacodynamics of MLN4924 [ Time Frame: Maximum duration of therapy for 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Disease response [ Time Frame: Day 21, every other cycle and end of study ] [ Designated as safety issue: No ]

Enrollment: 62
Study Start Date: April 2008
Study Completion Date: December 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

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

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00677170

Locations
United States, Georgia
Emory University Hospital
Atlanta, Georgia, United States, 30322
United States, Texas
Cancer Therapy & Research Center at the UT Health Science Center
San Antonio, Texas, United States, 78229
Institute for Drug Development
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00677170     History of Changes
Other Study ID Numbers: C15001
Study First Received: May 9, 2008
Last Updated: July 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on April 15, 2014