Advanced Non-Central Nervous System (CNS) MalignanciesPhase 1NCT02244112
A Phase 1 Study of Oprozomib to Assess Food Effect, Drug-Drug Interaction With Midazolam, and Safety and Tolerability in Patients With Advanced Malignancies
A Phase 1 study testing Oprozomib and Midazolam in people with Advanced Non-Central Nervous System (CNS) Malignancies, run by Amgen at 7 sites in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Non-Central Nervous System (CNS) Malignancies
- What is being tested?
- Oprozomib and Midazolam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 7 sitesUnited States
- Study dates
- Aug 2014to 10 Jul 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 9Show fewer
- 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.
Who cannot join
- 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.
Show all 25Show fewer
- 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.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Winship Cancer Institute
Atlanta, Georgia
University of Colorado Anschutz Medical Campus
Aurora, Colorado
Mary Crowley Cancer Research Centers - Medical City
Dallas, Texas
Henry Ford Hospital
Detroit, Michigan
University of Texas MD Anderson Cancer Center
Houston, Texas
Huntsman Cancer Institute
Salt Lake City, Utah
South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas
About this study
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
- Being tested
- Oprozomib, Midazolam
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OprozomibDrug
Subjects will receive oprozomib 270 mg per dose in Part I and oprozomib 300 mg per dose in Part II.
MidazolamDrug
Subjects will receive a single oral dose of midazolam 2 mg in Period 1 and oral midazolam 2 mg per dose in Period 2.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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. Receives: Drug: Oprozomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 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).
Measured: 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
Measured: 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.
Measured: 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.
Measured: Approximately 1 month
Secondary outcomes (1)
Adverse Events (AEs) and Serious Adverse Events (SAEs)
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).
Measured: Approximately 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2014 (estimated)
- Study startAug 2014
- Primary completion15 May 2015
- Study completion10 Jul 2019
Why it stopped: Why study stopped revised to "A program evaluation identified that the safety profile and pharmacokinetic (PK) characteristics of the formulation used in all oprozomib studies required further optimization and thus enrollment in OPZ009 was halted
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Non-Central Nervous System (CNS) MalignanciesStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02244112
- Sponsor's protocol ID
- OPZ009
- Status last verified
- Apr 2018
- First submitted
- 16 Sep 2014
- Last updated
- 21 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of Oprozomib to Assess Food Effect, Drug-Drug Interaction With Midazolam, and Safety and Tolerability in Patients With Advanced Malignancies
- ClinicalTrials.gov ID
- NCT02244112
- Acronym / sponsor ID
- OPZ009
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Why study stopped revised to "A program evaluation identified that the safety profile and pharmacokinetic (PK) characteristics of the formulation used in all oprozomib studies required further optimization and thus enrollment in OPZ009 was halted
- Enrolment
- 43 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- Aug 2014
- Primary completion
- 15 May 2015 (actual)
- Study completion
- 10 Jul 2019 (actual)
- First posted
- 18 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part I: Food Effect/QTc | Experimental | Drug: OprozomibSubjects 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 |
| Part II: Drug-Drug Interaction (DDI) | Experimental | Drug: Oprozomib, Drug: Midazolam* 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 |
| Extension | Experimental | Drug: OprozomibAfter 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OprozomibSubjects will receive oprozomib 270 mg per dose in Part I and oprozomib 300 mg per dose in Part II. | Drug | Extension, Part I: Food Effect/QTc, Part II: Drug-Drug Interaction (DDI) |
| MidazolamSubjects will receive a single oral dose of midazolam 2 mg in Period 1 and oral midazolam 2 mg per dose in Period 2. | Drug | Part II: Drug-Drug Interaction (DDI) |
Primary outcome
Food Effect/QTc - Cmax
Time frame: Approximately 5 days or up to 2 weeks
Pharmacokinetics (PK) parameter Cmax (maximum plasma concentration of oprozomib) between each diet (oprozomib under fasting versus low-fat, and fasting versus high-fat conditions).
Food Effect/QTc - AUC
Time frame: Approximately 5 days or up to 2 weeks
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).
Food Effect - tmax and t1/2
Time frame: Approximately 5 days or up to 2 weeks
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).
Food Effect - QT/QTc interval
Time frame: Approximately 5 days or up to 2 weeks
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
Drug-Drug Interaction (DDI) - Cmax
Time frame: Approximately 1 month
Pharmacokinetics (PK) parameter Cmax (maximum plasma concentration) of midazolam, in the presence and absence of oprozomib.
Drug-Drug Interaction (DDI) - AUC
Time frame: Approximately 1 month
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.
1 secondary outcome
Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Approximately 18 months
Results and safety
The study was stopped early (reason given: Why study stopped revised to "A program evaluation identified that the safety profile and pharmacokinetic (PK) characteristics of the formulation used in all oprozomib studies required further optimization and thus enrollment in OPZ009 was halted). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2021.
Related trials for Advanced Non-Central Nervous System (CNS) Malignancies
Active, not recruitingPhase 2
Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
Advanced Malignant Solid Neoplasm, Malignant Solid Neoplasm
Active, not recruitingPhase 2
Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
Advanced Malignant Solid Neoplasm, Recurrent Childhood Ependymoma
Active, not recruitingPhase 2
Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
Advanced Malignant Solid Neoplasm, Recurrent Ependymal Tumor
RecruitingPhase 1
A Phase 1/1b Study of IAM1363 in HER2 Cancers
HER2 Mutation-Related Tumors, HER2
Active, not recruitingPhase 1
A Study to Learn About the Study Medicine Called PF-07799544 as Monotherapy or in Combination in People With Advanced Solid Tumors
Melanoma, Glioma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Oprozomib and Midazolam in people with Advanced Non-Central Nervous System (CNS) Malignancies, run by Amgen at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Why study stopped revised to "A program evaluation identified that the safety profile and pharmacokinetic (PK) characteristics of the formulation used in all oprozomib studies required further optimization and thus enrollment in OPZ009 was halted). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Food Effect/QTc - Cmax (time frame: Approximately 5 days or up to 2 weeks). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2021.