A Safety and Efficacy Study of CC-122 in Combination With Nivolumab in Subjects With Unresectable Hepatocellular Carcinoma (HCC)
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|ClinicalTrials.gov Identifier: NCT02859324|
Recruitment Status : Active, not recruiting
First Posted : August 9, 2016
Last Update Posted : October 25, 2018
|Condition or disease||Intervention/treatment||Phase|
|Carcinoma, Hepatocellular||Drug: CC-122 Drug: Nivolumab||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||September 20, 2016|
|Estimated Primary Completion Date :||March 1, 2020|
|Estimated Study Completion Date :||March 1, 2020|
Experimental: CC-122 with Nivolumab
CC-122 orally 5/7 days with nivolumab Intravenously (IV) 3mg/kg every 2 weeks. Cohorts of up to 6 subjects per dose level until Recommended Phase 2 dose (RP2D).
- Dose Limiting Toxicity (DLT) [ Time Frame: Up to 28 days ]Number of participants with a DLT
- Adverse Events (AEs) [ Time Frame: Up to 27 months ]Number of participants with adverse events
- Overall Response Rate (ORR) - Phase 2 [ Time Frame: Up to 2 years ]The combined incidence of complete response (CR) + partial response (PR), by investigator assessment of response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- Disease control rate (DCR) [ Time Frame: Up to 2 years ]The combined incidence of CR, PR and stable disease by investigator assessment using RECIST 1.1.
- Duration of response (DoR) [ Time Frame: Up to 2 years ]Duration from the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date of recurrent or progressive disease using RECIST 1.1.
- Progression free survival (PFS) [ Time Frame: Up to 2 years ]Number of participants who survive without tumor progression using RECIST 1.1and time from the first dose date until the date of tumor progression or death, whichever occurs first.
- Overall survival (OS) [ Time Frame: Up to 2 years ]Number of participants who survive and the time from the first dose date until the date of death from any cause.
- Time to progression (TTP) [ Time Frame: Up to 2 years ]Time from the first dose date until the date of tumor progression using RECIST 1.1 (not including death).
- Pharmacokinetic - Cmax [ Time Frame: 0, 0.5, 1, 2, 4, 8 hours post dose on Cycle 1 Day 15 ]Maximum observed concentration
- Pharmacokinetic - AUC [ Time Frame: 0, 0.5, 1, 2, 4, 8 hours post dose on Cycle 1 Day 15 ]Area under the concentration time curve
- Pharmacokinetic - Tmax [ Time Frame: 0, 0.5, 1, 2, 4, 8 hours post dose on Cycle 1 Day 15 ]Time to maximum concentration
- Pharmacokinetic - t1/2 [ Time Frame: 0, 0.5, 1, 2, 4, 8 hours post dose on Cycle 1 Day 15 ]Terminal half-life
- Pharmacokinetic - CL/F [ Time Frame: 0, 0.5, 1, 2, 4, 8 hours post dose on Cycle 1 Day 15 ]Apparent total body clearance
- Pharmacokinetic - Vz/F [ Time Frame: 0, 0.5, 1, 2, 4, 8 hours post dose on Cycle 1 Day 15 ]Apparent volume of distribution
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02859324
|United States, California|
|UCLA Division of Hematology Oncology|
|Los Angeles, California, United States, 90095-1752|
|United States, Florida|
|University of Florida|
|Gainesville, Florida, United States, 32610|
|United States, New York|
|NYU Langone Medical Center|
|New York, New York, United States, 10016|
|United States, Texas|
|Mary Crowley Cancer Research|
|Dallas, Texas, United States, 75251|
|Institut Paoli Calmettes|
|Marseille Cedex 9, France, 13273|
|Centre Eugene Marquis|
|Rennes, France, 35200|
|Institut Universitaire du Cancer IUCT - Oncopole|
|Toulouse Cedex, France, 31059|
|Institut G. Roussy|
|Villejuif, France, 94800|
|IRCCS - Istituo Clinico Humanitas - Humanitas Cancer Center|
|Milan, Italy, 20089|
|Fondazione IRCCS Policlinico San Matteo|
|Pavia, Italy, 27100|
|Istituto Nazionale Tumori Regina Elena|
|Roma, Italy, 144|
|Hospital Universitario Vall D Hebron|
|Barcelona, Spain, 8035|
|Hospital Ramon y Cajal|
|Madrid, Spain, 28034|
|Hospital 12 de Octubre|
|Madrid, Spain, 28041|
|Study Director:||Alfredo Romano, MD, PhD||Celgene Corporation|