Clinical trial NCT01011530: Dose Escalation Study of MLN4924 in Adults With Melanoma
Official title: A Phase I, Open-Label, Dose Escalation Study of MLN4924, a Novel Inhibitor of Nedd8-Activating Enzyme, in Adult Patients With Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Melanoma
Keywords: Melanoma
Lead sponsor: Millennium Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2009-11-11
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

* 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) and inform recommended phase 2 dose of MLN4924
timeFrame: Up to 12 months of treatment
Secondary outcomes:
measure: Anti-tumor activities of MLN4924
timeFrame: Up to 12 months of treatment
measure: Pharmacodynamic effects of MLN4924 on blood and tumor cells
timeFrame: Primarily assessed during the first cycle of therapy
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: The Angeles Clinic and Research Institute
state: California
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: 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.