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

NCT ID: NCT02227914

Last Updated: 2017-05-02

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-31
• Study Completion Date: 2015-03-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Oprozomib with Sorafenib

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.

Group Type: EXPERIMENTAL

Oprozomib

Intervention Type: 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

Sorafenib

Intervention Type: DRUG

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

Sorafenib

Phase 2:

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

Group Type: ACTIVE_COMPARATOR

Sorafenib

Intervention Type: DRUG

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

Interventions

Oprozomib

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

Intervention Type: DRUG

Sorafenib

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients with advanced HCC

2. 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

3. Cirrhotic status of Child-Pugh Class A only

4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

5. 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

Exclusion Criteria

1. 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)

2. Renal failure requiring hemo- or peritoneal dialysis

3. History of cardiac disease

4. Active clinically serious infections. Hepatitis B is allowed if no active replication is present. Hepatitis C is allowed if no antiviral treatment is required

5. Known history of human immunodeficiency virus (HIV) infection

6. Known history or symptomatic metastatic brain or meningeal tumors

7. 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

8. History of organ allograft

9. Known or suspected allergy to the investigational agent or any agent given in association with this trial

10. 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

11. Uncontrolled diabetes

12. Any contraindication to oral hydration (e.g., preexisting cardiac impairment or fluid restriction)

13. Uncontrolled ascites

14. Pleural effusion or ascites that causes respiratory compromise (NCI-CTCAE ≥ Grade 2 dyspnea).

15. Women who are pregnant and/or breastfeeding

16. Prior use of any systemic anticancer chemotherapy for HCC

17. Prior use of systemic investigational agents for HCC

18. Concomitant treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors

19. Known hypersensitivity or intolerance to dexamethasone or 5-HT3 antagonist

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Lahey Hospital & Medical Center

Burlington, California, United States

Rocky Mountain Cancer Centers

Denver, Colorado, United States

University of Miami Hospital & Clinics

Miami, Florida, United States

The University of Chicago Medical Center

Chicago, Illinois, United States

The Ohio State University, Martha Morehouse Medical Plaza

Columbus, Ohio, United States

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

2014-003149-85

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

OPZ011

Identifier Type: -

Identifier Source: org_study_id