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

16 kwietnia 2021 zaktualizowane przez: 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.

Przegląd badań

Status

Zakończony

Warunki

Interwencja / Leczenie

Szczegółowy opis

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.

Typ studiów

Interwencyjne

Zapisy (Rzeczywisty)

21

Faza

  • Faza 2
  • Faza 1

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

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

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

18 lat i starsze (Dorosły, Starszy dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

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 studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Nie dotyczy
  • Model interwencyjny: Zadanie dla jednej grupy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: 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).
Lek: Niwolumab
Lek: CC-122

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Incidence of Dose Limiting Toxicities (DLTs)
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Disease Control Rate (DCR) by RECIST 1.1
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

Celgene

Śledczy

  • Dyrektor Studium: Akshay Patel, Celgene Corporation

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Rzeczywisty)

20 września 2016

Zakończenie podstawowe (Rzeczywisty)

27 marca 2020

Ukończenie studiów (Rzeczywisty)

27 marca 2020

Daty rejestracji na studia

Pierwszy przesłany

4 sierpnia 2016

Pierwszy przesłany, który spełnia kryteria kontroli jakości

4 sierpnia 2016

Pierwszy wysłany (Oszacować)

9 sierpnia 2016

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

11 maja 2021

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

16 kwietnia 2021

Ostatnia weryfikacja

1 kwietnia 2021

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

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

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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