Study of MLN4924 in Adult Patients With Nonhematologic Malignancies

NCT00677170 | Completed Phase 1

• 1 other identifier: C15001
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Advanced Nonhematologic Malignancies

Outcome Measures

Primary Outcomes (1)

• Determine the safety profile, MTD and PK/pharmacodynamics of MLN4924

  Maximum duration of therapy for 12 months

Secondary Outcomes (1)

• Disease response

  Day 21, every other cycle and end of study

Study Arms (1)

1

EXPERIMENTAL

MLN4924

Drug: MLN4924

Interventions

MLN4924 DRUG

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.

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (3)

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Cancer Therapy & Research Center at the UT Health Science Center

San Antonio, Texas, 78229, United States

Location

Institute for Drug Development

San Antonio, Texas, 78229, United States

Location

Related Publications (2)

• 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.

  PMID: 31355467 DERIVED

• Swords RT, Watts J, Erba HP, Altman JK, Maris M, Anwer F, Hua Z, Stein H, Faessel H, Sedarati F, Dezube BJ, Giles FJ, Medeiros BC, DeAngelo DJ. Expanded safety analysis of pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukemia and myelodysplastic syndromes. Blood Cancer J. 2017 Feb 3;7(2):e520. doi: 10.1038/bcj.2017.1. No abstract available.

  PMID: 28157218 DERIVED

MeSH Terms

Interventions

pevonedistat

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2008
• First Posted: May 14, 2008
• Study Start: April 1, 2008
• Primary Completion: February 1, 2012
• Study Completion: December 1, 2012
• Last Updated: July 16, 2013

Record last verified: 2013-07

Locations

US (3)