Study of MLN4924 in Adult Patients With Nonhematologic Malignancies

Millennium Pharmaceuticals

Status and phase

Completed

Phase 1

Conditions

Advanced Nonhematologic Malignancies

Treatments

Drug: MLN4924

Study type

Interventional

Funder types

Industry

Identifiers

NCT00677170

C15001

Details and patient eligibility

About

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.

Enrollment

62 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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