Safety and Efficacy Study of CC-122 Combined With Sorafenib for Primary Liver Cancer

NCT02323906 | Terminated Phase 1 DMC

• 1 other identifier: CC-122-HCC-001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 8

Brief Summary

CC-122-HCC-001 is a Phase 1b dose escalation and expansion clinical study of CC-122 in combination with sorafenib for subjects with unresectable HCC who have received no prior systemic therapy for HCC. The dose escalation phase of the study will explore several dose levels of CC-122 in combination with sorafenib, followed by an expansion part of the study using the optimal combination dose regimen.

Conditions

Carcinoma, Hepatocellular

Keywords

Hepatocellular; Carcinoma; Phase 1; CC-122; Sorafenib,; Nexavar; Unresectable Hepatocellular Carcinoma; Unresectable HCCAdvanced,; Hepatocellular Carcinoma; liver cancer

Outcome Measures

Primary Outcomes (2)

• Adverse Event

  Number of Participants with Adverse Events

  Up to 3 years

• Dose-Limiting Toxicity (DLT)

  Number of participants with a DLT. A DLT is defined as a treatment-related AE(s) occurring in Cycle 1 (including predose assessments on Cycle 2 Day 1).

  28 Days

Secondary Outcomes (6)

• Overall Response Rate (ORR)

  Up to 4 years

• Disease control rate (DCR)

  Up to 4 years

• Duration of response (DoR)

  Up to 4 years

• Progression-free survival

  Up to 4 years

• Overall survival

  Up to 4 years

Study Arms (1)

CC-122 + Fixed-dose Sorafenib

EXPERIMENTAL

A dose escalation and expansion clinical study of CC-122 in combination with sorafenib in subjects with unresectable HCC who have received no prior systemic therapy for HCC. The dose escalation part of the study will explore several dose levels of CC-122 in combination with sorafenib, followed by an expansion part.

Drug: CC-122; Drug: Sorafenib

Interventions

CC-122 DRUG

Investigational new drug

CC-122 + Fixed-dose Sorafenib

Sorafenib DRUG

Kinase inhibitor

Also known as: Nexavar

CC-122 + Fixed-dose Sorafenib

Eligibility Criteria

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

You may qualify if:

• Subject understands and voluntarily signs an informed consent document prior to conducting any study related assessments/procedures
• Subject is 18 years of age or more at the time of signing the Informed Consent Form
• Subject has a confirmed pathologic diagnosis of Hepatocellular carcinoma according to the American Association for the Study of Liver Diseases Guidelines.A biopsy performed at screening may serve as a diagnostic biopsy for subjects with radiographic diagnosis.
• Subject has unresectable stage B (intermediate), or C (advanced) Hepatocellular carcinoma according to the Barcelona Clinic Liver Cancer staging.Stage B subjects must have progressed after, or are not eligible for curative resection, transplantation, embolic, or ablative therapies
• Subject has at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1. Evaluable target lesions may not have been treated with local therapy; previously treated lesions may only be evaluated as target lesions if they are the only lesions available and have shown objective definite progression after prior treatment. Local therapy must have been completed at least four weeks prior to baseline tumor evaluation
• Satisfactory archival tumor biopsy tissue is retrieved, or new tumor biopsy is performed, prior to starting Cycle 1
• Subject has life expectancy of more than 12 weeks
• Subject has Eastern Cooperative Oncology Group Performance Status of 0 or 1
• Subject has Child-Pugh score of less than 7 (ie, class A or better) with neither encephalopathy nor clinically significant ascites (ascites requiring paracentesis within 3 months of signing the ICF is excluded). Child-Pugh status is calculated based on clinical findings and laboratory results during the screening period.
• Subject has the following laboratory parameters at screening:
• Adequate hematologic function including:
• Absolute Neutrophil Count of at least 1.5 x 109/L
• Platelets of at least 75,000 x 106/L
• Hemoglobin of at least 9 g/dL
• International Normalized Ratio of at least 1.7

You may not qualify if:

• LVEF (left ventricular ejection fraction) of 45% or less as determined by MUGA (multi-gated acquisition) or ECHO (Echocardiogram)
• Complete left bundle branch or bifascicular block
• Congenital long QT syndrome
• Persistent or clinically meaningful ventricular arrhythmias
• QTcF greater than 460 msec on Screening ECG (mean of triplicate recordings)
• Unstable angina pectoris or myocardial infarction less than 6 months prior to starting either study drug
• Uncontrolled hypertension (blood pressure greater than 140/90 mmHg on at least 2 measurements on sequential visits, despite blood pressure medication)
• Subjects with baseline blood pressure 140/90 mmHg are eligible but must have optimal medication for blood pressure management h. Troponin-T value more than the upper limit of normal or BNP greater than 100 pg/mL 18. Subject has acute or chronic active infectious disorders or uncontrolled nonmalignant illnesses whose control, in the opinion of the investigator, may be jeopardized by complications of this study therapy. Chronic hepatitis B and C virus (HBV and HCV) are excepted (ie, eligible for study); HBV requires antiviral therapy 19. Subject has undergone liver transplantation or other solid organ transplantation requiring immunosuppression 20. Subject is receiving chronic treatment with systemic corticosteroids or other potentially immunosuppressive agent. Intermittent topical or local injection of corticosteroids and oral/IV aldosterone or other mineralocorticoids is allowed 21. Subjects with history of non-healing wounds or ulcers, or bone fractures less than 3 months of a prior fracture 22. Subject is being treated with concomitant strong CYP3A4 inducers such as St. John's Wort, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital. The use of concomitant strong CYP3A4 inducers may decrease sorafenib plasma concentrations and must be avoided.
• \. Subject is a female who is pregnant or is breast feeding 24. Subject is unwilling or unable to comply with the protocol, in the opinion of the investigator 25. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study 26. Subject has any condition that confounds the ability to interpret data from the study

Sponsors & Collaborators

• Celgene: lead

Study Sites (8)

University of California San Francisco

San Francisco, California, 94115, United States

Location

University of Florida College of Med

Gainesville, Florida, 32610-0277, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202-528, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Greenville Hospital System

Greenville, South Carolina, 29605, United States

Location

University of Utah Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Carcinoma; Liver Neoplasms

Interventions

3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione; Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

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

• Kristen Hege, MD

  Celgene Corporation

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: November 24, 2014
• First Posted: December 24, 2014
• Study Start: January 16, 2015
• Primary Completion: December 21, 2016
• Study Completion: December 21, 2016
• Last Updated: March 20, 2017

Record last verified: 2017-03

Locations

US (8)