Dose Escalation Study of MLN4924 in Adults With Melanoma

NCT ID: NCT01011530

Last Updated: 2013-07-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2013-01-31

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.

Conditions

Metastatic Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MLN4924

MLN4924 via IV infusion

Group Type: EXPERIMENTAL

MLN4924

Intervention Type: DRUG

Patients will be administered MLN4924 via an IV infusion. Each 21-day treatment cycle is composed of 2 weeks intermittent dosing of MLN4924 on Days 1, 4, 8 and 11, followed by a rest period of 10 days. A cohort of patients will receive a reduced first dose on Day 1, approximately half the strength of the dose received on Days 4, 8, 11 and dose will not be administered on Day 4 if the Day 1 dose is not tolerated.(Schedule A ramp-up), or continuous weekly dosing (Days 1, 8, and 15) of MLN4924 (Schedule B)

Interventions

MLN4924

Patients will be administered MLN4924 via an IV infusion. Each 21-day treatment cycle is composed of 2 weeks intermittent dosing of MLN4924 on Days 1, 4, 8 and 11, followed by a rest period of 10 days. A cohort of patients will receive a reduced first dose on Day 1, approximately half the strength of the dose received on Days 4, 8, 11 and dose will not be administered on Day 4 if the Day 1 dose is not tolerated.(Schedule A ramp-up), or continuous weekly dosing (Days 1, 8, and 15) of MLN4924 (Schedule B)

Intervention Type: DRUG

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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

The Angeles Clinic and Research Institute

Santa Monica, California, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 31355467 (View on PubMed)

Other Identifiers

C15005

Identifier Type: -

Identifier Source: org_study_id