A Phase 1 Study of Oprozomib to Assess Food Effect, Drug-Drug Interaction With Midazolam, and Safety and Tolerability in Patients With Advanced Malignancies

NCT02244112 | Terminated Phase 1 DMC

• 1 other identifier: OPZ009
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 7

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 tolerability of oprozomib in patients with advanced malignancies

Conditions

Advanced Non-Central Nervous System (CNS) Malignancies

Outcome Measures

Primary Outcomes (6)

• Food Effect/QTc - Cmax

  Pharmacokinetics (PK) parameter Cmax (maximum plasma concentration of oprozomib) between each diet (oprozomib under fasting versus low-fat, and fasting versus high-fat conditions).

  Approximately 5 days or up to 2 weeks

• Food Effect/QTc - AUC

  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).

  Approximately 5 days or up to 2 weeks

• Food Effect - tmax and t1/2

  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).

  Approximately 5 days or up to 2 weeks

• Food Effect - QT/QTc interval

  QT/QTc interval will be extracted from continuous ECGs performed during each period in the Food Effect/QTc part of the study: * Twelve (12)-lead ECGs will be serially recorded digitally and read centrally * The RR, PR and QT intervals and QRS duration will be analyzed * QTc will be calculated using Bazett's and Fridericia's formulas

  Approximately 5 days or up to 2 weeks

• Drug-Drug Interaction (DDI) - Cmax

  Pharmacokinetics (PK) parameter Cmax (maximum plasma concentration) of midazolam, in the presence and absence of oprozomib.

  Approximately 1 month

• Drug-Drug Interaction (DDI) - AUC

  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.

  Approximately 1 month

Secondary Outcomes (1)

• Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Approximately 18 months

Other Outcomes (2)

• Overall Response Rate (ORR)

  Approximately 18 months

• Time To Progression (TTP)

  Approximately 18 months

Study Arms (3)

Part I: Food Effect/QTc

EXPERIMENTAL

Subjects will receive a single dose of oprozomib 270 mg in 1 of 3 fasting/fed conditions: * Diet A: Fasted conditions * Diet B: A low-fat breakfast. A low-fat breakfast is defined as having a total caloric value of less than 400 calories, with less than 20% from fat * Diet C: A high-fat breakfast. A high-fat breakfast is defined as having a total caloric value of 800 to 1000 calories, with approximately 50% from fat

Drug: Oprozomib

Part II: Drug-Drug Interaction (DDI)

EXPERIMENTAL

* Period 1: Midazolam 2 mg single oral dose on one day between Day -7 and -4 * Period 2: Midazolam 2 mg single oral dose 1 hour following oprozomib dose on Day 1 of Cycle 1 and Day 2 of Cycle 2. Oprozomib 300 mg dose on Days 1, 2, 8 and 9 of Cycles 1 and Cycle 2

Drug: Oprozomib; Drug: Midazolam

Extension

EXPERIMENTAL

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.

Drug: Oprozomib

Interventions

Oprozomib DRUG

Subjects will receive oprozomib 270 mg per dose in Part I and oprozomib 300 mg per dose in Part II.

Extension; Part I: Food Effect/QTc; Part II: Drug-Drug Interaction (DDI)

Midazolam DRUG

Subjects will receive a single oral dose of midazolam 2 mg in Period 1 and oral midazolam 2 mg per dose in Period 2.

Part II: Drug-Drug Interaction (DDI)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (7)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

Location

Winship Cancer Institute

Atlanta, Georgia, United States

Location

Henry Ford Hospital

Detroit, Michigan, United States

Location

Mary Crowley Cancer Research Centers - Medical City

Dallas, Texas, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Location

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

ONX 0912; Midazolam

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2014
• First Posted: September 18, 2014
• Study Start: August 1, 2014
• Primary Completion: May 15, 2015
• Study Completion: July 10, 2019
• Last Updated: February 21, 2021

Record last verified: 2018-04

Locations

US (7)