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

16 avril 2021 mis à jour par: 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.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Réel)

21

Phase

  • Phase 2
  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

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

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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).
Médicament: Nivolumab
Médicament: CC-122

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Incidence of Dose Limiting Toxicities (DLTs)
Délai: 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)
Délai: 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)
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Disease Control Rate (DCR) by RECIST 1.1
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Celgene

Les enquêteurs

  • Directeur d'études: Akshay Patel, Celgene Corporation

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

20 septembre 2016

Achèvement primaire (Réel)

27 mars 2020

Achèvement de l'étude (Réel)

27 mars 2020

Dates d'inscription aux études

Première soumission

4 août 2016

Première soumission répondant aux critères de contrôle qualité

4 août 2016

Première publication (Estimation)

9 août 2016

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

11 mai 2021

Dernière mise à jour soumise répondant aux critères de contrôle qualité

16 avril 2021

Dernière vérification

1 avril 2021

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

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

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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