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

16 april 2021 uppdaterad av: Celgene

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

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.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Faktisk)

21

Fas

  • Fas 2
  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Frankrike
      • Marseille Cedex 9, Frankrike, 13273
        • Institut Paoli Calmettes
      • Rennes, Frankrike, 35200
        • Centre Eugene Marquis
      • Toulouse Cedex, Frankrike, 31059
        • Institut Universitaire du Cancer IUCT - Oncopole
      • Villejuif CEDEX, Frankrike, 94805
        • Institut Gustave Roussy Hematologie
  • Förenta staterna
    • California
      • Los Angeles, California, Förenta staterna, 90095-1752
        • UCLA Division of Hematology Oncology
    • Florida
      • Gainesville, Florida, Förenta staterna, 32610
        • University of Florida
    • New York
      • New York, New York, Förenta staterna, 10016
        • NYU Langone Medical Center
    • Texas
      • Dallas, Texas, Förenta staterna, 75251
        • Mary Crowley Cancer Research
  • Italien
      • Milan, Italien, 20089
        • IRCCS - Istituo Clinico Humanitas - Humanitas Cancer Center
      • Pavia, Italien, 27100
        • Fondazione IRCCS Policlinico San Matteo
      • Roma, Italien, 144
        • Istituto Nazionale Tumori Regina Elena
  • Spanien
      • Barcelona, Spanien, 8035
        • Hospital Universitario Vall D hebron
      • Madrid, Spanien, 28034
        • Hospital Ramon y Cajal
      • Madrid, Spanien, 28041
        • Hospital 12 de Octubre

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: N/A
  • Interventionsmodell: Enskild gruppuppgift
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: 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).
Läkemedel: Nivolumab
Läkemedel: CC-122

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Incidence of Dose Limiting Toxicities (DLTs)
Tidsram: 28 days

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
Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs)
Tidsram: From first dose up to 28 days (CC-122) or 90 days (nivolumab) post-last dose (up to 2 years)

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)
Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Tidsram: up to 2 years
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

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Disease Control Rate (DCR) by RECIST 1.1
Tidsram: up to 2 years
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
Duration of Response (DoR) by RECIST 1.1
Tidsram: up to 2 years
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
Progression-Free Survival (PFS) by RECIST 1.1
Tidsram: up to 2 years

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
Overall Survival (OS) by RECIST 1.1
Tidsram: up to 2 years

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
Time to Progression (TTP) by RECIST 1.1
Tidsram: up to 2 years

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
Maximum Observed Concentration (Cmax)
Tidsram: 28 days
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
Area Under the Concentration Time Curve (AUC)
Tidsram: 28 days
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
Time to Maximum Concentration (Tmax)
Tidsram: 28 days
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
Terminal Half-life (T-HALF)
Tidsram: 28 days
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
Apparent Volume of Distribution (Vz/F)
Tidsram: 28 days
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

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Celgene

Utredare

  • Studierektor: Akshay Patel, Celgene Corporation

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

20 september 2016

Primärt slutförande (Faktisk)

27 mars 2020

Avslutad studie (Faktisk)

27 mars 2020

Studieregistreringsdatum

Först inskickad

4 augusti 2016

Först inskickad som uppfyllde QC-kriterierna

4 augusti 2016

Första postat (Uppskatta)

9 augusti 2016

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

11 maj 2021

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

16 april 2021

Senast verifierad

1 april 2021

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • CC-122-HCC-002
  • 2016-000112-15 (EudraCT-nummer)

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