A Study to Evaluate the Effects of Pevonedistat on the Corrected QT (QTc) Interval in Participants With Advanced Solid Tumors



Status:Recruiting
Healthy:No
Age Range:18 - Any
Updated:9/12/2018
Start Date:November 15, 2017
End Date:January 5, 2020
Contact:Takeda Study Registration Call Center
Email:globaloncologymedinfo@takeda.com
Phone:+1-866-835-2233

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

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.

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.
We found this trial at
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Dallas, Texas 75231
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3550 Jerome Avenue
Bronx, New York 10467
(718) 920-4321
Montefiore Medical Center As the academic medical center and University Hospital for Albert Einstein College...
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Bronx, NY
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10900 Euclid Ave
Cleveland, Ohio 44106
216-368-2000
Case Western Reserve Univ Continually ranked among America's best colleges, Case Western Reserve University has...
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2799 W Grand Blvd
Detroit, Michigan 48202
(313) 916-2600
Henry Ford Hospital Founded in 1915 by auto pioneer Henry Ford and now one of...
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8503 Arlington Blvd., Ste. 400
Fairfax, Virginia 22031
(703) 280-5390
Virginia Cancer Specialists, PC Now the world's most advanced cancer treatment capabilities can be found...
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Fairfax, VA
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940 NE 13th St
Oklahoma City, Oklahoma 73190
(405) 271-6458
University of Oklahoma Health Sciences Center The OU Health Sciences Center is composed of seven...
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Santa Monica, California 90403
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Tampa, Florida 33612
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Tampa, FL
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