Clinical Trial 19497

Cancer Type:
Interventions:MLN4924 (Pevonedistat); Paraplatin (carboplatin); Pevonedistat; Taxol (paclitaxel); Taxotere (docetaxel); carboplatin; docetaxel; paclitaxel

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • Solmaz Sahebjam

Overview

Study Title

A Randomized, Crossover Phase 1 Study to Evaluate the Effects of Pevonedistat on the QTc Interval in Patients With Advanced Solid Tumors

Summary

The purpose of this study is to characterize the effects of 25 and 50 milligram per square meter (mg/m^2) pevonedistat on the Fridericia corrected QT interval (QTcF) of the electrocardiogram (ECG).

Objective

Primary Objective: The primary objective of this study is to characterize the effects of 25 and 50 mg/m^2 pevonedistat on the Fridericia corrected QT interval (QTcF) of the ECG. Secondary Objectives: The secondary objectives for Part A of this study are as follows: To assess the effects of pevonedistat on individual corrected QT interval (QTcI), QRS, PR, and HR following a single IV dose at 25 and 50 mg/m^2. To characterize the PK profile of pevonedistat following a single IV dose at 25 and 50 mg/m^2. The secondary objective for Part B of this study is to evaluate the disease response that may be observed after treatment with pevonedistat in combination with either docetaxel or carboplatin+paclitaxel in patients with advanced solid tumors. Safety Objectives: The safety objective for Part A is to evaluate the safety and tolerability of pevonedistat in patients with advanced solid tumors following a single IV dose at 25 and 50 mg/m^2. The safety objective for Part B is to evaluate the safety and tolerability of pevonedistat in combination with either docetaxel or carboplatin+paclitaxel in patients with advanced solid tumors.

Inclusion Criteria

  • Participants must have a histologically or cytologically confirmed metastatic or locally advanced solid tumor(s) appropriate for treatment with one of the 2 combination therapies in Part B of this study, have progressed despite standard therapy, or for whom conventional therapy is not considered effective.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  • Expected survival longer than 3 months from enrollment in the study.
  • Recovered (that is, grade less than or equal to 1 toxicity) from the reversible effects of prior anticancer therapy.
  • Suitable venous access for the study-required blood sampling (including pharmacokinetic [PK] sampling). Entry Criteria for Continuation to Optional Part B: After completing Part A of the study, participants may choose to enter the optional Part B of the study. To be eligible for the optional Part B, participants must have completed Part A and be reassessed to determine if they meet the entry criteria for optional Part B. Only participants who meet the following criteria may enter into Part B:
  • ECOG performance status of 0 to 1.
  • Absolute neutrophil count (ANC) greater than or equal to (>=) 1500 per cubic millimeter (/mm^3).
  • Platelet count >=100,000/mm^3.
  • Laboratory values for hemoglobin, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and serum creatinine or calculated/measured creatinine clearance.
  • Diarrhea symptoms resolved to Grade 1 or better.
  • QTc interval less than 480 millisecond (msec).
  • Computed tomography (CT) scan or magnetic resonance imaging (MRI) of the chest, abdomen, and pelvis within 28 days of Cycle 1 Day 1.

  • Exclusion Criteria

  • Treatment with strong cytochrome P3A (CYP3A) inducers within 14 days before the first dose of pevonedistat. Participants must have no history of amiodarone use within 6 months before the first dose of pevonedistat nor require the use of these medications during the study.
  • Treatment with QT-prolonging drugs with a risk of causing torsades de pointes (TdP. Participants taking drugs with a possible or conditional risk of QT prolongation or drugs that are to be avoided by participants with congenital long QT syndrome may be considered if on a stable dose, pending discussion and agreement between the investigator and the sponsor.
  • History of Brugada syndrome, risk factors for TdP, or family history of long QT syndrome.
  • Implantable cardioverter defibrillator.
  • Cardiac pacemaker with heart rate (HR) set at a fixed rate and treatment with concomitant medication that may limit increase in HR in response to hypotension (example, high-dose beta blocker).
  • Known moderate to severe aortic stenosis, moderate to severe mitral stenosis, or other valvulopathy (ongoing).
  • Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.