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Dose Escalation Study of MLN4924 in Adults With Melanoma

Primary Purpose

Metastatic Melanoma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

MLN4924

About this trial

This is an interventional treatment trial for Metastatic Melanoma focused on measuring Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

The Angeles Clinic and Research Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

MLN4924

Arm Description

MLN4924 via IV infusion

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose (MTD) and inform recommended phase 2 dose of MLN4924

Secondary Outcome Measures

Anti-tumor activities of MLN4924

Pharmacodynamic effects of MLN4924 on blood and tumor cells

Full Information

NCT ID

NCT01011530

First Posted

November 9, 2009

Last Updated

July 15, 2013

Sponsor

Millennium Pharmaceuticals, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01011530

Brief Title

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

2. Study Status

Record Verification Date

July 2013

Overall Recruitment Status

Completed

Study Start Date

December 2009 (undefined)

Primary Completion Date

May 2012 (Actual)

Study Completion Date

January 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Millennium Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Melanoma

Keywords

Melanoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

37 (Actual)

8. Arms, Groups, and Interventions

Arm Title

MLN4924

Arm Type

Experimental

Arm Description

MLN4924 via IV infusion

Intervention Type

Drug

Intervention Name(s)

MLN4924

Intervention Description

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)

Primary Outcome Measure Information:

Title

Maximum Tolerated Dose (MTD) and inform recommended phase 2 dose of MLN4924

Time Frame

Up to 12 months of treatment

Secondary Outcome Measure Information:

Title

Anti-tumor activities of MLN4924

Time Frame

Up to 12 months of treatment

Title

Pharmacodynamic effects of MLN4924 on blood and tumor cells

Time Frame

Primarily assessed during the first cycle of therapy

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Monitor

Organizational Affiliation

Millennium Pharmaceuticals, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

The Angeles Clinic and Research Institute

City

Santa Monica

State/Province

California

ZIP/Postal Code

90404

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

31355467

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.

Results Reference

derived

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Dose Escalation Study of MLN4924 in Adults With Melanoma

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