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

NCT02227914 | Withdrawn Phase 1 DMC

• 2 other identifiers: OPZ0112014-003149-85
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 6

Brief 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). 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.

Conditions

Advanced Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (2)

• 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).

  16 months

• 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.

  16 months

Secondary Outcomes (6)

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

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

• Pharmacokinetics (PK) parameters - Phase 1b

  16 months

• Pharmacodynamic (PDn) parameter - Phase 1b

  16 months

• Overall Response Rate (ORR) - Phase 2

  16 months

• Progression-free Survival (PFS) - Phase 2

  16 months

Study Arms (2)

Oprozomib with Sorafenib

EXPERIMENTAL

Phase 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.

Drug: Oprozomib; Drug: Sorafenib

Sorafenib

ACTIVE COMPARATOR

Phase 2: Study subjects who meet the entry criteria will receive sorafenib 400 mg twice a day (800 mg total daily dose).

Drug: Sorafenib

Interventions

Oprozomib DRUG

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

Oprozomib with Sorafenib

Sorafenib DRUG

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

Oprozomib with Sorafenib; Sorafenib

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (6)

Lahey Hospital & Medical Center

Burlington, California, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, United States

Location

University of Miami Hospital & Clinics

Miami, Florida, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, United States

Location

The Ohio State University, Martha Morehouse Medical Plaza

Columbus, Ohio, United States

Location

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Location

MeSH Terms

Interventions

ONX 0912; Sorafenib

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: August 26, 2014
• First Posted: August 28, 2014
• Study Start: December 1, 2014
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: May 2, 2017

Record last verified: 2017-04

Locations

US (6)