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

Stopped early · Phase 1

Conditions studied: Carcinoma, Hepatocellular

In brief

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.

Key facts

Study ID

NCT02323906

Run by

Celgene

People needed

12

Starts

2015-01-16

Expected to finish

2016-12-21

Last updated by the study team

2017-03-20

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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
• Adequate hepatic function including:
• Serum aspartate aminotransferase and alanine amino-transferase of at least 5 times the upper limit of normal
• Serum total bilirubin of at least 3 mg/dL
• Serum albumin of at least 2.8 g/dL Note: Laboratories in combination must still be Child Pugh score less than 7
• Other laboratory parameters:
• Serum creatinine of at least 1.5 times the upper limit of normal
• Potassium within normal range or corrected with supplements
• For subjects with known or suspected cirrhosis, esophagogastroduodenoscopy ) within 12 months of signing the informed consent form, showing no evidence of untreated varices or stigmata of active bleeding (such as active ulcer, visible vessel, or blood) is required.
• Subjects with history of upper GI bleeding must have an EGD of 3 months or less prior to signing the consent form confirming adequate prior endoscopic therapy (eg, no evidence of any untreated varices, recent or active bleeding, stigmata suggesting high risk for bleeding, active ulcer). Subjects with history/suspected esophageal varices must be on optimal medical management (eg, proton pump inhibitor and non-selective beta-blocker) per local institutional policy.
• Subject is able to adhere to the study visit schedule and other protocol requirements

You may not qualify if…

• 1. Subject has received previous systemic therapy for Hepatocellular carcinoma including sorafenib, chemotherapy and investigational agents 2. Subject has received any local anticancer therapy ≤ 4 weeks prior to baseline tumor evaluation 3. Subject has undergone major surgery within the last 4 weeks or minor surgery within the last 2 weeks prior to signing the Informed Consent Form or who have not recovered from surgery 4. Subject has received an investigational drug or therapy for disease other than Hepatocellular carcinoma within the last 4 weeks or 5 half-lives, whichever is shorter, prior to signing the Informed Consent Form 5. Subject has completed any radiation treatment less than 2 weeks prior to signing the Informed Consent Form 6. Subject has received the last dose of α-interferon, ribavirin, sofobuvir and/or other antiviral therapies for Hepatitis C Virus (HCV) less than 4 weeks prior to signing the Informed Consent Form 7. Subject has any clinically significant bleeding, including bleeding from esophageal/gastric varices within ≤ 3 months of signing the informed consent form, which required transfusion, surgical procedure or hospitalization. Esophageal varices should be treated according to local standard practice (eg, ligation or banding and procedure completed ≤ 3 months prior to signing the informed consent form). See Inclusion Criterion 10 8. Subjects requiring therapeutic anticoagulation with either warfarin or low molecular weight heparin. Low dose low molecular weight heparin for catheter maintenance are permitted 9. Subject has tumor invasion of stomach or duodenum 10. Subject has histologic proof of fibrolamellar carcinoma 11. Subjects with known symptomatic brain metastasis 12. Subject has persistent diarrhea due to a malabsorptive syndrome (such as celiac sprue or inflammatory bowel disease) malabsorption ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03) Grade 2, despite medical management, or any other significant GI disorder that could affect the absorption of either study drug 13. Subject has history of concurrent second cancers requiring active, ongoing systemic treatment. 14. Subject has a known history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not mandatory) 15. Subject has peripheral neuropathy of at least NCI CTCAE Grade 2 16. Subject has a history of persistent skin rash of at least NCI CTCAE Grade 2 17. Subject has impaired cardiac function or clinically significant cardiac disease including any of the following:
• 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

Where it is running

• University of California San Francisco — San Francisco, California, United States
• University of Florida College of Med — Gainesville, Florida, United States
• Moffitt Cancer Center — Tampa, Florida, United States
• Indiana University Cancer Center — Indianapolis, Indiana, United States
• Henry Ford Hospital — Detroit, Michigan, United States
• Greenville Hospital System — Greenville, South Carolina, United States
• University of Utah Huntsman Cancer Institute — Salt Lake City, Utah, United States
• Seattle Cancer Care Alliance — Seattle, Washington, United States

Full record on ClinicalTrials.gov

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