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Advanced Hepatocellular CarcinomaPhase 1/2NCT02227914

Phase 1b/2 Study of Oprozomib in Combination With Sorafenib in Subjects With Advanced Hepatocellular Carcinoma

A Phase 1/2 study testing Oprozomib and Sorafenib in people with Advanced Hepatocellular Carcinoma, run by Amgen at 6 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The purpose of Phase 1b of the study is to determine the maximum tolerated dose, pharmacokinetics (PK) and pharmacodynamics (PDn) and assess the safety, tolerability and activity of oprozomib in combination with sorafenib in subjects with advanced hepatocellular carcinoma (HCC). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Hepatocellular Carcinoma
What is being tested?
Oprozomib and Sorafenib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
6 sitesUnited States
Study dates
Dec 2014to Mar 2015
Phase
Phase 1/2
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

  • Patients with advanced HCC
  • For the Phase 2 portion of the study, at least 1 measurable tumor lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, which has not been previously treated with local therapy
  • Cirrhotic status of Child-Pugh Class A only
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • The following laboratory parameters:
  • Albumin ≥ 2.8 g/dL
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  • Platelet count ≥ 60,000/mm3
  • Absolute neutrophil count (ANC) ≥ 1500/mm3
  • Hemoglobin ≥ 8.5 g/dL
  • Total bilirubin ≤ 3 mg/dL
  • Alanine aminotransaminase (ALT) and aspartate aminotransferase (AST) ≤ 3 times upper limit of normal (ULN)
  • Amylase and lipase ≤ 1.5 times ULN
  • Calculated or measured creatinine clearance (CrCl) ≥ 30 mL/min
  • Prothrombin time (PT)-international normalized ratio (INR) ≤ 2.3 or PT ≤ 6 seconds above control

Who cannot join

  • Previous or concurrent cancer that is distinct in primary site or histology from HCC, EXCEPT cervical and breast carcinoma in situ, adequately treated basal cell or squamous cell carcinoma of the skin, or superficial bladder tumors (Ta, Tis \& T1)
  • Renal failure requiring hemo- or peritoneal dialysis
  • History of cardiac disease
  • Active clinically serious infections. Hepatitis B is allowed if no active replication is present. Hepatitis C is allowed if no antiviral treatment is required
  • Known history of human immunodeficiency virus (HIV) infection
  • Known history or symptomatic metastatic brain or meningeal tumors
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  • Clinically significant gastrointestinal (GI) bleeding, serious nonhealing wound and ulcer within 3 months prior to study entry, or bone fracture within 30 days prior to study entry
  • History of organ allograft
  • Known or suspected allergy to the investigational agent or any agent given in association with this trial
  • Inability to swallow medication, inability or unwillingness to comply with the drug administration requirements, or GI condition that could interfere with the oral absorption or tolerance of treatment
  • Uncontrolled diabetes
  • Any contraindication to oral hydration (e.g., preexisting cardiac impairment or fluid restriction)
  • Uncontrolled ascites
  • Pleural effusion or ascites that causes respiratory compromise (NCI-CTCAE ≥ Grade 2 dyspnea).
  • Women who are pregnant and/or breastfeeding
  • Prior use of any systemic anticancer chemotherapy for HCC
  • Prior use of systemic investigational agents for HCC
  • Concomitant treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors
  • Known hypersensitivity or intolerance to dexamethasone or 5-HT3 antagonist

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Lahey Hospital & Medical Center

    Burlington, California

  • The University of Chicago Medical Center

    Chicago, Illinois

  • The Ohio State University, Martha Morehouse Medical Plaza

    Columbus, Ohio

  • Rocky Mountain Cancer Centers

    Denver, Colorado

  • University of Wisconsin Comprehensive Cancer Center

    Madison, Wisconsin

  • University of Miami Hospital & Clinics

    Miami, Florida

Other trials in United States

About this study

The purpose of Phase 1b of the study is to determine the maximum tolerated dose, pharmacokinetics (PK) and pharmacodynamics (PDn) and assess the safety, tolerability and activity of oprozomib in combination with sorafenib in subjects with advanced hepatocellular carcinoma (HCC).

The purpose of Phase 2 of the study is to evaluate the efficacy of oprozomib in combination with sorafenib versus sorafenib alone and to compare the key outcome measures for subjects with advanced HCC.

Being tested
Oprozomib, Sorafenib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OprozomibDrug

    Study subjects will receive oprozomib tablets once a day on Days 1, 2, 8, 9, 15, 16, 22 and 23 of a 28 day cycle

  • SorafenibDrug

    Study subjects will receive sorafenib tablets twice a day for Days 1-28

Study groups in NCT02227914
Study groupRoleWhat they receive
Oprozomib with SorafenibExperimentalPhase 1b: Oprozomib doses will be escalated in sequential groups of at least 2 subjects. Study subjects will receive oprozomib at dose levels of 90, 120, 150, 180, 210, or 240 mg + sorafenib to reach the dose levels of 600 or 800 mg total daily dose until the maximum tolerated dose (MTD) is reached. Phase 2: Study subjects who meet the entry criteria will receive oprozomib + sorafenib at the RP2D (recommended Phase 2 dose) established in the Phase 1b portion of the study.
Receives: Drug: Oprozomib; Drug: Sorafenib
SorafenibActive comparatorPhase 2: Study subjects who meet the entry criteria will receive sorafenib 400 mg twice a day (800 mg total daily dose).
Receives: Drug: Sorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) - Phase 1b

    To determine the maximum tolerated dose (MTD) and identify the recommended Phase 2 dose (RP2D) of oprozomib in combination with sorafenib in subjects with advanced hepatocellular carcinoma (HCC).

    Measured: 16 months

  2. Time To Progression (TTP) - Phase 2

    To evaluate the efficacy of oprozomib in combination with sorafenib versus sorafenib alone in subjects with advanced HCC, as measured by time to progression (TTP), defined as time from randomization to disease progression.

    Measured: 16 months

Secondary outcomes (6)

  1. Adverse Events (AEs) and Serious Adverse Events (SAEs) - Phase 1b & Phase 2

    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: Until 30 days after the end of study (32 months)

  2. Pharmacokinetics (PK) parameters - Phase 1b

    Evaluate population pharmacokinetic (PK) parameters, including maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), area under the curve at the last measurable time point (AUC0-t), and area under the curve extrapolated to infinity (AUC0-inf) using noncompartmental methods.

    Measured: 16 months

  3. Pharmacodynamic (PDn) parameter - Phase 1b

    The extent of inactivation of proteasome activity in red blood cells (RBCs) after oprozomib dosing will be monitored as a PDn parameter. Pharmacodynamic inhibition will be listed by dose cohort, exposure, and response status.

    Measured: 16 months

  4. Overall Response Rate (ORR) - Phase 2

    To estimate the overall response rate (ORR), defined as the proportion of subjects with a best overall response of complete response (CR) and partial response (PR) for subjects receiving oprozomib in combination with sorafenib and for subjects receiving sorafenib alone.

    Measured: 16 months

  5. Progression-free Survival (PFS) - Phase 2

    Progression-free survival (PFS), defined as time from randomization to the earlier of PD or death due to any cause.

    Measured: 16 months

  6. Overall Survival (OS) - Phase 2

    Overall survival (OS) is defined as time from randomization to death due to any cause.

    Measured: 16 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Aug 2014 (estimated)
  2. Study startDec 2014
  3. Primary completionMar 2015
  4. Study completionMar 2015

Why it stopped: Study stopped due to administrative reasons

Resources

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02227914
Sponsor's protocol ID
OPZ011
Other IDs
2014-003149-85, 2014
Status last verified
Apr 2017
First submitted
26 Aug 2014
Last updated
2 May 2017
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Oprozomib and Sorafenib in people with Advanced Hepatocellular Carcinoma, run by Amgen at 6 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 14 inclusion and 19 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: withdrawn, as of the sponsor's last update on 2 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 withdrawn before enrolling participants, so there are no results.

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?

Maximum Tolerated Dose (MTD) - Phase 1b (time frame: 16 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02227914.

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 2 May 2017.

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