Status:
TERMINATED
A Phase 1 Study of Oprozomib to Assess Food Effect, Drug-Drug Interaction With Midazolam, and Safety and Tolerability in Patients With Advanced Malignancies
Lead Sponsor:
Amgen
Conditions:
Advanced Non-Central Nervous System (CNS) Malignancies
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
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 tolerabi...
Eligibility Criteria
Inclusion
- Key
- 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
- 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.
Key Trial Info
Start Date :
August 1 2014
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
July 10 2019
Estimated Enrollment :
43 Patients enrolled
Trial Details
Trial ID
NCT02244112
Start Date
August 1 2014
End Date
July 10 2019
Last Update
February 21 2021
Active Locations (7)
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1
University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States
2
Winship Cancer Institute
Atlanta, Georgia, United States
3
Henry Ford Hospital
Detroit, Michigan, United States
4
Mary Crowley Cancer Research Centers - Medical City
Dallas, Texas, United States