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

Advanced Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02227914
• Other study ID #: OPZ011
• Secondary ID: 2014-003149-85
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• First received: August 26, 2014
• Last updated: April 28, 2017
• Start date: December 2014
• Est. completion date: March 2015

Study information

• Verified date: April 2017
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key 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

Key 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

Related Conditions & MeSH terms

• Advanced Hepatocellular Carcinoma
• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Drug:
• 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
• Sorafenib
Study subjects will receive sorafenib tablets twice a day for Days 1-28

Locations

Country	Name	City	State
United States	Lahey Hospital & Medical Center	Burlington	California
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	The Ohio State University, Martha Morehouse Medical Plaza	Columbus	Ohio
United States	Rocky Mountain Cancer Centers	Denver	Colorado
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	University of Miami Hospital & Clinics	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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).	Until 30 days after the end of study (32 months)
Secondary	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.	16 months
Secondary	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.	16 months
Secondary	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.	16 months
Secondary	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.	16 months
Secondary	Overall Survival (OS) - Phase 2	Overall survival (OS) is defined as time from randomization to death due to any cause.	16 months