Pevonedistat Alone and in Combination With Chemotherapy in Patients With Mesothelioma

NCT03319537 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: 17-361
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this study is to test any good and bad effects of activity pevonedistat taken alone, and also to test the safety of pevonedistat in combination with standard chemotherapy, pemetrexed/cisplatin.

Conditions

Mesothelioma

Keywords

Pevonedistat; Pemetrexed; Cisplatin; 17-361

Outcome Measures

Primary Outcomes (2)

• Number of Patients Who Have a Clinical Benefit Rate (CBR) (Cohort 1)

  The CBR is defined as the proportion of patients CR, PR or SD at 18 weeks based on RECIST criteria.

  at 18 weeks post initiation of treatment

• Maximum Tolerated Dose (MTD) (Cohort 2)

  If none of the initial cohort of 3 has a dose-limited toxicity the dose level will be escalated. If one has a DLT that dose level will be expanded with 3 more patients. Dose escalation will stop if ≥2 DLTs are seen at a dose level. The MTD is defined as the highest dose level at which no more than 1 of the 6 patients at that level has a DLT. If no patient in the 3-patient cohort has a DLT and the dose level is under final consideration of the MTD, an additional three patients will be treated at that level for confirmation.

  3 year

Study Arms (2)

Pevonedistat

EXPERIMENTAL

Drug: pevonedistat

pevonedistat in combination with pemetrexed and cisplatin

EXPERIMENTAL

Drug: pevonedistat; Drug: Pemetrexed and cisplatin

Interventions

pevonedistat DRUG

Pevonedistat will be administered as an IV infusion at a dose of 50 mg/m2 days 1, 3, and 5 of a 21-day cycle.Treatment will be administered as an outpatient.

Pevonedistat; pevonedistat in combination with pemetrexed and cisplatin

Pemetrexed and cisplatin DRUG

Pemetrexed, 500 mg/m2 and cisplatin, 75 mg/m2, will be given at fixed doses on day 1 of each cycle.

pevonedistat in combination with pemetrexed and cisplatin

Eligibility Criteria

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

You may qualify if:

• Both cohorts:
• Patients must have a histologically confirmed diagnosis of epithelioid, sarcomatoid, or mixed-type malignant pleural or peritoneal mesothelioma that is not amenable to surgery.
• Patients must have measurable disease according to the modified RECIST criteria for pleural mesothelioma, or standard RECIST for peritoneal mesothelioma. Patients must have adequate tissue sample available for molecular profiling with MSK-IMPACT (archived tissue block or 15-20 unstained slides). Patients will sign a separate informed document (IRB #12-245) to allow this to be performed.
• Patients must be at least 18 years of age.
• Karnofsky performance status ≥ 70%.
• Adequate renal function: serum creatinine ≤ 1.5 x ULN.
• Clinical laboratory values within the following parameters (repeat if more than 7 days before the first dose):
• °Albumin \> 2.7 g/dL
• Patients must have adequate hepatic function as defined by:
• AST and ALT ≤ 2.5 x ULN
• Total bilirubin ≤ upper limit of normal (ULN) except in patients with Gilbert's syndrome. Patients with Gilbert's syndrome may enroll if direct bilirubin ≤1.5 x ULN of the direct bilirubin.
• Patients must have adequate bone marrow function as defined by:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
• Platelets ≥ 100 x 10\^9/L
• Hemoglobin ≥ 9 g/dL.

You may not qualify if:

• Patients currently receiving radiation therapy, or who have received radiation within 2 weeks from the start of therapy. Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study.
• Diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone resection.
• Life-threatening illness unrelated to cancer.
• Patients with uncontrolled coagulopathy or bleeding disorder.
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• Known cardiopulmonary disease defined as:
• Unstable angina
• Congestive heart failure (New York Hear Association \[NYHA\] Class III or IV
• Myocardial infarction (MI) within 6 months prior to first dose (patients who had ischemic heart disease such as ACS, MI and/or revascularization greater than 6 months before screening and who are without cardiac symptoms may enroll.
• Cardiomyopathy
• Clinically significant arrhythmia:
• Polymorphic ventricular fibrillation or torsade de pointes.
• Permanent atrial fibrillation \[a fib\], defined as continuous a fib ≥ 6 months.
• Persistent a fib, defined as sustained a fib lasting \> 7 days and/or requiring cardioversion in the 4 weeks before screening
• Grade 3 a fib defined as symptomatic and incompletely controlled medically, or controlled with device (e.g. pacemaker), or ablation

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• M.D. Anderson Cancer Center: collaborator

Study Sites (8)

Memorial Sloan Kettering at Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Rockville Centre

Rockville Centre, New York, 11570, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Mesothelioma

Interventions

pevonedistat; Pemetrexed; Cisplatin

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Dr. Marjorie Zauderer, MD
• Organization: Memorial Sloan Kettering Cancer Center

zauderem@mskcc.org

646-608-3790

Study Officials

• Majorie Zauderer, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Model Details: This study is a single institution trial with two cohorts to test the efficacy of the NEDD8 inhibitor, pevonedistat as a single agent in patients with NF2 mutant MM (Cohort 1), and also to test the safety of pevonedistat in combination with standard chemotherapy, pemetrexed/cisplatin (Cohort 2).

Study Record Dates

• First Submitted: October 20, 2017
• First Posted: October 24, 2017
• Study Start: October 5, 2017
• Primary Completion: June 5, 2023
• Study Completion: June 5, 2023
• Last Updated: May 23, 2024
• Results First Posted: May 23, 2024

Record last verified: 2024-04

Locations

US (8)