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).
The drug being tested in this study is called pevonedistat. Pevonedistat in combination with standard of care will be used to treat participants who have advanced solid tumors. This study will assess the effects of pevonedistat on the QTc interval in participants with advanced solid tumors. The study will enroll approximately 45 participants. The study will be conducted in two Parts: Part A and Part B. Part A will have a 2-way crossover design and will involve the collection of triplicate ECGs. In Part A, participants will be randomly assigned to one of the two treatment groups as follow: * Pevonedistat 25 mg/m\^2 + Pevonedistat 50 mg/m\^2 * Pevonedistat 50 mg/m\^2 + Pevonedistat 25 mg/m\^2 Eligible participants from Part A will continue treatment in optional Part B with pevonedistat in combination with SoC, docetaxel or carboplatin plus paclitaxel. The investigator will decide which pevonedistat combination a participant will receive. * Pevonedistat 25 mg/m\^2 + Docetaxel * Pevonedistat 20 mg/m\^2 + Carboplatin + Paclitaxel This multi-center trial will be conducted in the United States. The overall time to participate in this study is 9.6 months. Participants will make a final visit to the clinic 30 days after receiving their last dose of study drug for a follow-up assessment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
68
Pevonedistat intravenous infusion.
Docetaxel intravenous infusion.
Carboplatin intravenous infusion.
Sarcoma Oncology Center
Santa Monica, California, United States
Moffitt Cancer Center
Tampa, Florida, United States
Henry Ford Hospital
Detroit, Michigan, United States
Montefiore Medical Center
The Bronx, New York, United States
Part A: Change From Time-matched Baseline in Fridericia-corrected QT Interval (QTcF) After Pevonedistat Administration
Change from time-matched baseline in QTcF was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m\^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m\^2 or 50 mg/m\^2 on Day 1 while others received treatment on Day 8. Data is reported at pre-dose and at multiple timepoints (1, 2, 3, 4, 6, 9, 11 and 24 hours) postdose up to Day 8 in Part A. Analysis of variance (ANOVA) was used for the analysis.
Time frame: Baseline up to Day 8
Part A: Change From Time-matched Baseline in Individual Corrected QT Interval (QTcI) After Pevonedistat Administration
Change from time-matched baseline in QTcI was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m\^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m\^2 or 50 mg/m\^2 on Day 1 while others received treatment on Day 8. ANOVA was used for the analysis.
Time frame: Predose, and at multiple time points up to 24 hours post dose on Day 1 or Day 8 in Part A
Part A: Change From Time-matched Baseline in QRS After Pevonedistat Administration
Change from time-matched baseline in QRS was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m\^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m\^2 or 50 mg/m\^2 on Day 1 while others received treatment on Day 8. ANOVA was used for the analysis.
Time frame: Predose, and at multiple time points post dose up to 24 hours on Day 1 or Day 8 in Part A
Part A: Change From Time-matched Baseline in PR After Pevonedistat Administration
Change from time-matched baseline in PR was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m\^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m\^2 or 50 mg/m\^2 on Day 1 while others received treatment on Day 8. ANOVA was used for the analysis.
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Paclitaxel intravenous infusion.
Case Western Reserve University
Cleveland, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Mary Crowley Medical Research
Dallas, Texas, United States
Virginia Cancer Specialists
Fairfax, Virginia, United States
Time frame: Predose, and at multiple time points post dose up to 24 hours on Day 1 or Day 8 in Part A
Part A: Change From Time-matched Baseline in Heart Rate (HR) After Pevonedistat Administration
Change from time-matched baseline in HR was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m\^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m\^2 or 50 mg/m\^2 on Day 1 while others received treatment on Day 8. ANOVA was used for the analysis.
Time frame: Predose, and at multiple time points post dose up to 24 hours on Day 1 or Day 8 in Part A
Part A: Cmax: Maximum Observed Plasma Concentration for Pevonedistat
Time frame: Days 1 or 8 predose and at multiple time points (up to 24 hours) post dose in Part A
Part A: AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Postdose for Pevonedistat
Time frame: Days 1 or 8 predose and at multiple time points (up to 24 hours) post dose in Part A
Part A: Terminal Phase Elimination Half-life (t1/2) for Pevonedistat
Time frame: Days 1 or 8 predose and at multiple time points (up to 24 hours) post dose in Part A
Part B: Overall Response Rate (ORR)
Percentage of participants who achieve an overall response per investigator's assessment at end of treatment,according to Response Evaluation Criteria in Solid Tumor(RECIST),version 1.1 guideline. Complete response(CR):Disappearance of all target lesions.Any pathological lymph nodes(whether target and non target)must have reduction in short axis to \<10 millimeter(mm).Partial Response(PR):atleast 30% decrease in sum of diameter of target lesions,taking as reference baseline sum of diameter.Stable Disease(SD):Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression(PD),taking as reference smallest sum of diameter; PD:atleast 20% increase in sum of diameter of target lesions,taking as reference,smallest sum on study(this includes baseline sum if that is smallest on study).In addition to relative increase of 20%,sum must also demonstrate an absolute increase of atleast 5 mm.Appearance of 1 or more new lesions is also considered progression.
Time frame: Up to Cycle 45 (end of treatment) (Cycle length=21 days)