- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02244112
A Phase 1 Study of Oprozomib to Assess Food Effect, Drug-Drug Interaction With Midazolam, and Safety and Tolerability in Patients With Advanced Malignancies
February 18, 2021 updated by: Amgen
The purpose of this Phase 1 of the study is to evaluate the effect of food on the pharmacokinetics (PK) of oprozomib, the drug-drug interaction of oprozomib with midazolam, and the safety and tolerability of oprozomib in patients with advanced malignancies
Study Overview
Status
Terminated
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
43
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Colorado
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Aurora, Colorado, United States
- University of Colorado Anschutz Medical Campus
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Georgia
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Atlanta, Georgia, United States
- Winship Cancer Institute
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Michigan
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Detroit, Michigan, United States
- Henry Ford Hospital
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Texas
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Dallas, Texas, United States
- Mary Crowley Cancer Research Centers - Medical City
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Houston, Texas, United States
- University of Texas MD Anderson Cancer Center
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San Antonio, Texas, United States
- South Texas Accelerated Research Therapeutics, LLC
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Utah
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Salt Lake City, Utah, United States
- Huntsman Cancer Institute
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Key Inclusion Criteria:
- Histologically confirmed diagnosis of an advanced malignancy.
- Relapsed after standard therapy for their malignancy, or if no standard therapy is defined, relapsed after investigational therapy and considered by the treating physician to be an appropriate candidate for a Phase 1 clinical study
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
- Adequate hepatic function, with bilirubin ≤ 1.5 times the upper limit of normal (ULN) in the absence of Gilbert's disease or hemolysis, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times ULN.
- Absolute neutrophil count (ANC) ≥ 1000/mm3. Screening ANC must be independent of myeloid growth factor support for at least 1 week, or pegylated growth factors for 2 weeks.
- Hemoglobin > 7g/dL. Patients may receive red blood cell (RBC) transfusions or erythropoietin or darbepoetin in accordance with institutional guidelines up to 1 week before screening.
- Platelet count > 30,000 mm3. Patients will not have received platelet transfusions for at least 1 week before screening.
- Uric acid, if elevated, must be lowered to less than the ULN.
- Calculated or measured creatinine clearance (CrCl) ≥ 30 mL/min calculated using the formula of Cockcroft and Gault [(140 - age) × mass (kg) / (72 × serum creatinine mg/dL)]. Multiply result by 0.85 if female.
Key Exclusion Criteria:
- Recovered (i.e., ≤ Grade 1 toxicity or patient's baseline status) from the reversible nonhematologic effects of prior anticancer therapy, excluding alopecia.
- Systemic chemotherapy with approved or investigational anticancer therapeutics, including steroid therapy intended to treat underlying malignancy, within 3 weeks before the first oprozomib dose; for antibody therapy, a minimum of 3 half-lives must elapse before the first oprozomib dose.
- Radiation therapy within 3 weeks before first oprozomib dose. Radioimmunotherapy within 8 weeks before first oprozomib dose.
- Autologous stem cell transplant (ASCT) within 8 weeks and allogeneic SCT within 16 weeks prior to initiation of study treatment. Patients with prior allogeneic SCT must not have evidence of moderate-to-severe graft-versus-host disease (as defined in Filipovich 2005).
- Unresolved toxicity (NCI-CTCAE version 4.03) ≥ Grade 2 from previous anticancer therapy, except alopecia.
- Major surgery within 3 weeks before first oprozomib dose.
- Congestive heart failure (New York Heart Association Class III to IV)
- Symptomatic cardiac ischemia.
- Conduction abnormalities uncontrolled by conventional intervention, including but not limited to persistent or permanent atrial fibrillation.
- History of ventricular fibrillation or ventricular tachycardia.
- History of torsade de pointe.
- Myocardial infarction within 6 months before first dose.
- Abnormal measurements on 12-lead ECG.
- Uncontrolled diabetes mellitus or hypertension
- Dysphagia or inability to swallow tablets.
- Insufficiency of the exocrine pancreas, steatorrhea, or other disorders of the digestive system that impair absorption.
- Resection of any portion of the stomach or intestines, with the exception of appendectomy.
- History of bariatric surgery, except in cases where no bowel was resected and all devices have been removed.
- Active infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks before first dose, unless cultures or polymerase chain reaction (PCR) have been negative for 14 days.
- Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive, or suspected hepatitis C infection.
- Primary malignancy of the central nervous system.
- Patient has symptomatic brain metastasis. Patients with brain metastases must have stable neurologic status following surgery or radiation for at least 2 weeks after completion of the definitive therapy, AND be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- Significant peripheral neuropathy (Grade 2 with pain or ≥ Grade 3).
- Systemic treatment with strong inhibitors of P-glycoprotein ([P-gp]; i.e., itraconazole, ketoconazole) within 14 days before the first dose of oprozomib.
- Patients must not have used any potent CYP3A4 inhibitors (i.e., ketoconazole) within 7 days prior to enrollment, or any potent CYP3A4 inducers (i.e., rifampin) within 14 days prior to enrollment.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Part I: Food Effect/QTc
Subjects will receive a single dose of oprozomib 270 mg in 1 of 3 fasting/fed conditions:
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Subjects will receive oprozomib 270 mg per dose in Part I and oprozomib 300 mg per dose in Part II.
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Experimental: Part II: Drug-Drug Interaction (DDI)
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Subjects will receive oprozomib 270 mg per dose in Part I and oprozomib 300 mg per dose in Part II.
Subjects will receive a single oral dose of midazolam 2 mg in Period 1 and oral midazolam 2 mg per dose in Period 2.
|
Experimental: Extension
After subjects complete the Food Effect/QTc or DDI part, subjects may participate in the extension part of the study, where oprozomib treatment will be continued on Days 1, 2, 8, and 9 of each 14-day cycle.
During this part of the study, it is recommended that oprozomib be taken with food.
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Subjects will receive oprozomib 270 mg per dose in Part I and oprozomib 300 mg per dose in Part II.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Food Effect/QTc - Cmax
Time Frame: Approximately 5 days or up to 2 weeks
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Pharmacokinetics (PK) parameter Cmax (maximum plasma concentration of oprozomib) between each diet (oprozomib under fasting versus low-fat, and fasting versus high-fat conditions).
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Approximately 5 days or up to 2 weeks
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Food Effect/QTc - AUC
Time Frame: Approximately 5 days or up to 2 weeks
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Pharmacokinetics (PK) parameter AUC (area under the concentration-time curve from time zero to the last measurable time point [AUC0-t], area under the concentration-time curve from time zero to infinity [AUC0-inf]) of oprozomib between each diet (oprozomib under fasting versus low-fat, and fasting versus high-fat conditions).
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Approximately 5 days or up to 2 weeks
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Food Effect - tmax and t1/2
Time Frame: Approximately 5 days or up to 2 weeks
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Pharmacokinetics (PK) parameters tmax (time to reach maximum plasma concentration) and t1/2 (terminal half-life) between each diet (oprozomib under fasting versus low-fat, and fasting versus high-fat conditions).
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Approximately 5 days or up to 2 weeks
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Food Effect - QT/QTc interval
Time Frame: Approximately 5 days or up to 2 weeks
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QT/QTc interval will be extracted from continuous ECGs performed during each period in the Food Effect/QTc part of the study:
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Approximately 5 days or up to 2 weeks
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Drug-Drug Interaction (DDI) - Cmax
Time Frame: Approximately 1 month
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Pharmacokinetics (PK) parameter Cmax (maximum plasma concentration) of midazolam, in the presence and absence of oprozomib.
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Approximately 1 month
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Drug-Drug Interaction (DDI) - AUC
Time Frame: Approximately 1 month
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Pharmacokinetics (PK) parameter AUC (area under the concentration-time curve from time zero to the last measurable time point [AUC0-t], area under the concentration-time curve from time zero to infinity [AUC0-inf]) of midazolam, in the presence and absence of oprozomib.
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Approximately 1 month
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Approximately 18 months
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Number of patients that experience Adverse Events (AEs).
Adverse Events (AEs) and Serious Adverse Events (SAEs) graded according to the NCI-CTCAE (Version 4.03).
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Approximately 18 months
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate (ORR)
Time Frame: Approximately 18 months
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Overall Response Rate (ORR) according to disease-specific response criteria
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Approximately 18 months
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Time To Progression (TTP)
Time Frame: Approximately 18 months
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Time to progression (TTP) according to disease-specific evaluation criteria
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Approximately 18 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
August 1, 2014
Primary Completion (Actual)
May 15, 2015
Study Completion (Actual)
July 10, 2019
Study Registration Dates
First Submitted
September 16, 2014
First Submitted That Met QC Criteria
September 16, 2014
First Posted (Estimate)
September 18, 2014
Study Record Updates
Last Update Posted (Actual)
February 21, 2021
Last Update Submitted That Met QC Criteria
February 18, 2021
Last Verified
April 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Tranquilizing Agents
- Psychotropic Drugs
- Hypnotics and Sedatives
- Adjuvants, Anesthesia
- Anti-Anxiety Agents
- GABA Modulators
- GABA Agents
- Midazolam
Other Study ID Numbers
- OPZ009
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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