Clinical trial NCT02859324: A Safety and Efficacy Study of CC-122 in Combination With Nivolumab in Subjects With Unresectable Hepatocellular Carcinoma (HCC)
Official title: A Phase 1/2, MultiCenter, Open-label, Dose Finding Study to Assess the Safety, Tolerability and Preliminary Efficacy of CC-122 in Combination With Nivolumab in Subjects With Unresectable Hepatocellullar Carcinoma (HCC) Following First Line Treatment Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Carcinoma, Hepatocellular
Keywords: CC-122
Nivolumab
Hepatocellular Carcinoma
Phase 1/2
Safety
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2016-08-09
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: CC-122-HCC-002 is a Phase 1/2 dose escalation and expansion clinical study of CC-122 in combination with nivolumab in subjects with unresectable hepatocellular carcinoma (HCC) who have progressed after or were intolerant to no more than 2 previous systemic therapies for unresectable HCC, or are naïve to systemic therapy.

Detailed description: Study population included subjects who had progressed after or were intolerant to no more than 2 previous systemic therapies for unresectable HCC, or are naïve to systemic therapy.

The dose escalation part of the study was designed to explore three dose levels of CC-122 to identify the recommended phase 2 dose (RP2D) to be used in the expansion phase. Approximately 20 subjects were to be enrolled in the dose escalation part of the study. Subjects could be treated for up to 2 years, or until progression of disease, unacceptable toxicity, subject/physician decision, withdrawal of consent, death. Safety follow up until 28 days after CC122 treatment and 90 days after nivolumab treatment. RECIST 1.1 criteria was used to determine response. Survival follow up until death, withdrawal of consent, or the study closes. Subjects were permitted to continue treatment beyond progression (TBP) if they continue to meet protocol criteria, had stable performance status, had clinical benefit, other treatment options were discussed. A separate ICF was signed to continue TBP.

During the dose escalation phase, CC-122 was administered orally 5 consecutive days out of 7 (5 days on/2 days off weekly) on Days 1 to 5, 8 to 12, 15 to 19 and 22 to 26 of each 28-day cycle. Once the RP2D for dosing of CC-122 in combination with nivolumab was defined, expansion (Phase 2) would start. A modified 3+3 dose escalation design was used to identify the initial toxicity of the combination. Up to six subjects were concurrently enrolled into a dose level. Decisions as to which dose level to enroll a new subject were based on the number of subjects enrolled and evaluable, the number of subjects experiencing DLTs, and the number of subjects enrolled but who are not yet evaluable for toxicity in the current cohort at the time of new subject entry. A Safety Review Committee (SRC) comprised of investigators participating in the study made dose escalation decisions based on these criteria.

After completion of the Dose Escalation Phase, the Dose Expansion Phase of the study did not proceed due to the changing landscape in the treatment of HCC. There were no additional safety concerns or safety signals identified in the dose escalation phase of the study.

Eligibility criteria: Inclusion Criteria:

* Subjects must satisfy the following criteria to be enrolled in the study:
* Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF)
* Subject has a confirmed pathologic diagnosis of Hepatocellular carcinoma (HCC) according to the American Association for the Study of Liver Diseases (AASLD) Guidelines.
* Subjects who have progressed after or were intolerant to no more than 2 previous systemic therapies for unresectable HCC, or are naïve to systemic therapy.
* Subject has at least one measurable lesion according to RECIST 1.1.
* Subject has a life expectancy of ≥ 12 weeks
* Subject has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
* Subject has adequate hematologic function and adequate hepatic function at screening

Exclusion Criteria:

* The presence of any of the following will exclude a subject from enrollment:
* Subject has received more than 2 previous systemic therapies for Hepatocellular carcinoma (HCC).
* Subject has received previous treatment with any anti-PD-1 (Programmed death 1) or anti-PD-L1 (PD-1 ligand receptor) antibody

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities (DLTs)
timeFrame: 28 days
measure: Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From first dose up to 28 days (CC-122) or 90 days (nivolumab) post-last dose (up to 2 years)
measure: Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: up to 2 years
Secondary outcomes:
measure: Disease Control Rate (DCR) by RECIST 1.1
timeFrame: up to 2 years
measure: Duration of Response (DoR) by RECIST 1.1
timeFrame: up to 2 years
measure: Progression-Free Survival (PFS) by RECIST 1.1
timeFrame: up to 2 years
measure: Overall Survival (OS) by RECIST 1.1
timeFrame: up to 2 years
measure: Time to Progression (TTP) by RECIST 1.1
timeFrame: up to 2 years
measure: Maximum Observed Concentration (Cmax)
timeFrame: 28 days
measure: Area Under the Concentration Time Curve (AUC)
timeFrame: 28 days
measure: Time to Maximum Concentration (Tmax)
timeFrame: 28 days
measure: Terminal Half-life (T-HALF)
timeFrame: 28 days
measure: Apparent Volume of Distribution (Vz/F)
timeFrame: 28 days
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Division of Hematology Oncology
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Marseille Cedex 9
country: France
facility: Institut Paoli Calmettes
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Toulouse Cedex
country: France
facility: Institut Universitaire du Cancer IUCT - Oncopole
city: Villejuif CEDEX
country: France
facility: Institut Gustave Roussy Hematologie
city: Milan
country: Italy
facility: IRCCS - Istituo Clinico Humanitas - Humanitas Cancer Center
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Roma
country: Italy
facility: Istituto Nazionale Tumori Regina Elena
city: Barcelona
country: Spain
facility: Hospital Universitario Vall D Hebron
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
Study officials:
affiliation: Celgene Corporation
name: Akshay Patel
role: STUDY_DIRECTOR
References: