Study of MLN4924 in Adult Patients With Nonhematologic Malignancies

Advanced Nonhematologic Malignancies Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00677170
• Other study ID #: C15001
• Status: Completed
• Phase: Phase 1
• First received: May 9, 2008
• Last updated: July 15, 2013
• Start date: April 2008
• Est. completion date: December 2012

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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: December 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Nonhematologic Malignancies
• Neoplasms

Intervention

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.

Locations

Country	Name	City	State
United States	Emory University Hospital	Atlanta	Georgia
United States	Cancer Therapy & Research Center at the UT Health Science Center	San Antonio	Texas
United States	Institute for Drug Development	San Antonio	Texas

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	Determine the safety profile, MTD and PK/pharmacodynamics of MLN4924		Maximum duration of therapy for 12 months	Yes
Secondary	Disease response		Day 21, every other cycle and end of study	No