A Safety and Efficacy Study of CC-122 in Combination With Nivolumab in Subjects With Unresectable Hepatocellular Carcinoma (HCC)

Carcinoma, Hepatocellular Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02859324
• Other study ID #: CC-122-HCC-002
• Secondary ID: 2016-000112-15
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 20, 2016
• Est. completion date: March 27, 2020

Study information

• Verified date: April 2021
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: March 27, 2020
• Est. primary completion date: March 27, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Drug:
• CC-122

• Nivolumab

Locations

Country	Name	City	State
France	Institut Paoli Calmettes	Marseille Cedex 9
France	Centre Eugene Marquis	Rennes
France	Institut Universitaire du Cancer IUCT - Oncopole	Toulouse Cedex
France	Institut Gustave Roussy Hematologie	Villejuif CEDEX
Italy	IRCCS - Istituo Clinico Humanitas - Humanitas Cancer Center	Milan
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	Istituto Nazionale Tumori Regina Elena	Roma
Spain	Hospital Universitario Vall D Hebron	Barcelona
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Ramon y Cajal	Madrid
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	University of Florida	Gainesville	Florida
United States	UCLA Division of Hematology Oncology	Los Angeles	California
United States	NYU Langone Medical Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  France,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Dose Limiting Toxicities (DLTs)	During dose escalation, the DLT assessment period is defined as Days 1 to 28 of Cycle 1 including the predose assessments specified for Day 1 of Cycle 2.; A DLT is defined as any of the following toxicities occurring within the DLT assessment window unless the event can clearly be determined to be unrelated to the drug.	28 days
Primary	Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs)	During dose escalation, the TEAE phase 1 assessment period is defined as Days 1 to 28 of Cycle 1 including the predose assessments specified for Day 1 of Cycle 2.; Number of participants who experienced a TEAE during the course of the study.	From first dose up to 28 days (CC-122) or 90 days (nivolumab) post-last dose (up to 2 years)
Primary	Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	ORR is is defined as the number and percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR).	up to 2 years
Secondary	Disease Control Rate (DCR) by RECIST 1.1	DCR is is defined as the number and percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) or stable disease (SD).	up to 2 years
Secondary	Duration of Response (DoR) by RECIST 1.1	Duration of response is measured from the date the criterion is first met for CR/PR using RECIST 1.1 rules (whichever is first recorded) until the first date when progressive disease using RECIST 1.1 is documented or death occurred.	up to 2 years
Secondary	Progression-Free Survival (PFS) by RECIST 1.1	Progression-Free Survival (PFS) is defined as the time from the first dose date of study drug until tumor progression or death, whichever occurs first. A subject who has neither progressed nor died or who progresses or dies after an extended lost-to-follow up time (two or more missed assessments) is censored on the date of last adequate tumor assessment. Subjects without valid baseline or post-baseline tumor assessments are censored on their first dose date.; Median and the 2-sided 95% confidence interval (CI) are based on Kaplan-Meier estimate of progression-free survival and time to progression using both observed and censored data.	up to 2 years
Secondary	Overall Survival (OS) by RECIST 1.1	Overall Survival (OS) is measured as the time from the first dose of study drug to death from any cause. Participants who have no death reported are censored at the last contact date the participant is known to be alive.; Median and the 2-sided 95% confidence interval (CI) are based on Kaplan-Meier estimate of progression-free survival and time to progression using both observed and censored data.	up to 2 years
Secondary	Time to Progression (TTP) by RECIST 1.1	Time to Progression (TTP) is defined as the time from the first dose date of study drug until tumor progression; TTP does not include death. The censoring rules are the same as PFS except that deaths without progression are censored at last adequate tumor assessment.; Median and the 2-sided 95% confidence interval (CI) are based on Kaplan-Meier estimate of progression-free survival and time to progression using both observed and censored data.	up to 2 years
Secondary	Maximum Observed Concentration (Cmax)	Blood was collected according to intensive and sparse sampling strategies to estimate the population pharmacokinetic (PK) of CC-122 when administered in combination with nivolumab.	28 days
Secondary	Area Under the Concentration Time Curve (AUC)	Blood was collected according to intensive and sparse sampling strategies to estimate the population pharmacokinetic (PK) of CC-122 when administered in combination with nivolumab.	28 days
Secondary	Time to Maximum Concentration (Tmax)	Blood was collected according to intensive and sparse sampling strategies to estimate the population pharmacokinetic (PK) of CC-122 when administered in combination with nivolumab.	28 days
Secondary	Terminal Half-life (T-HALF)	Blood was collected according to intensive and sparse sampling strategies to estimate the population pharmacokinetic (PK) of CC-122 when administered in combination with nivolumab.	28 days
Secondary	Apparent Volume of Distribution (Vz/F)	Blood was collected according to intensive and sparse sampling strategies to estimate the population pharmacokinetic (PK) of CC-122 when administered in combination with nivolumab.	28 days