A Study to Evaluate the Effects of Pevonedistat on the Corrected QT (QTc) Interval in Participants With Advanced Solid Tumors
Condition: Advanced Solid Neoplasm
Intervention: Pevonedistat; Docetaxel; Carboplatin; Paclitaxel
Intervention description: Pevonedistat intravenous infusion.; Docetaxel intravenous infusion.; Carboplatin intravenous infusion.; Paclitaxel intravenous infusion.
Intervention MeSH terms: Paclitaxel; Docetaxel; Carboplatin; Pevonedistat
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 68.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug therapy

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).
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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.

          2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

          3. Expected survival longer than 3 months from enrollment in the study.

          4. Recovered (that is, grade less than or equal to [<=] 1 toxicity) from the reversible
             effects of prior anticancer therapy.

          5. Suitable venous access for the study-required blood sampling (including
             pharmacokinetic [PK] sampling).

        Exclusion Criteria:

          1. 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.

          2. 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.

          3. History of Brugada syndrome, risk factors for TdP, or family history of long QT
             syndrome.

          4. Implantable cardioverter defibrillator.

          5. 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).

          6. Known moderate to severe aortic stenosis, moderate to severe mitral stenosis, or other
             valvulopathy (ongoing).

          7. Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.

        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 <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.