- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT07715903
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Phase I Study Evaluating Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Background:
Cancers that begin in the colon, adrenal glands, or bile ducts may spread to the liver. These liver tumors are often treated using a hepatic artery infusion (HAI) pump. The HAI pump is installed in the artery that goes to the liver; drugs are administered directly to the liver through this pump. But these tumors often return after treatment. Carfilzomib (CFZ) is a drug approved to treat another kind of cancer. Researchers want to find out if this drug may be helpful when administered through the HAI pump directly to the liver for people with colon, adrenal glands, or bile duct cancer that has spread to the liver.
Objective:
To test the safety of carfilzomib (CFZ) delivered via a hepatic artery infusion (HAI) pump directly to the liver in people with cancer in their liver.
Eligibility:
People aged 18 years or older with cancers of the colon, adrenal glands, or bile ducts that spread to the liver and persist after treatment. They must have a functioning hepatic artery infusion (HAI) pump in place from previous treatment of HAI pump therapy.
Design:
Participants will be screened. They will have a physical exam, blood tests, imaging scans, and a test of their heart function. They will also have a test to show how the blood flows through their liver: A radioactive substance will be injected into a vein, and a special camera will take pictures of the blood flow for up to 1 hour.
Participants will receive the study drug for about 6 months. They will visit the clinic once a week. Their HAI pump will be filled with the drug at each visit; the drug will slowly drain from the pump into the liver. Blood tests and imaging scans will be repeated during the study.
Participants will have follow-up visits 1 and 3 months after their last dose of study drug.
An optional liver biopsy (tissue sample) for research purposes may be done before the study drug is given, and again (optional) within 28 days after first receiving the study drug. Individuals may participate in the study even if they do not agree to have the biopsies done.
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Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
Background:
- Targeting protein homeostasis with proteasome inhibitors has demonstrated excellent efficacy across multiple pre-clinical cancer models, although translation to patients with solid tumors has consistently failed to yield meaningful responses secondary to new protein synthesis rebound associated with intermittent dosing.
- Implantable pumps for outpatient continuous infusion were developed and culminated in a commercialized product in 1980, though the only drug used to date is floxuridine.
- Carfilzomib (CFZ), a second-generation irreversible 20S core particle proteasome inhibitor, can be delivered by the hepatic artery infusion pump to diminish extra-hepatic systemic clearance and feasibly direct a larger percentage of the total dose to the desired tissues at continuous concentrations.
Objective:
-To establish the safety of hepatic artery infusion (HAI) of carfilzomib (CFZ) in participants with liver metastatic disease who were previously treated with HAI pump therapy
Eligibility:
- Participants with colorectal cancer (CRC), intrahepatic cholangiocarcinoma (ICC), or adrenocortical carcinoma (ACC) with liver metastatic disease not amenable to resection
- Participants must have been treated with HAI floxuridine and already have a surgically inserted HAI pump in place
- Age >= 18 years
- Adequate organ function
Design:
- Open-label, single-center, non-randomized Phase I study
- Treatment with HAI infusion of CFZ will be delivered in cycles of 28 days for up to 6 cycles.
Tipo di studio
Iscrizione (Stimato)
Fase
- Fase 1
Contatti e Sedi
Contatto studio
- Nome: Kathleen M Smith, R.N.
- Numero di telefono: (240) 858-3531
- Email: kathleen.smith3@nih.gov
Backup dei contatti dello studio
- Nome: Jonathan M Hernandez, M.D.
- Numero di telefono: (240) 760-6072
- Email: jonathan.hernandez@nih.gov
Luoghi di studio
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Maryland
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Bethesda, Maryland, Stati Uniti, 20892
- National Institutes of Health Clinical Center
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Contatto:
- National Cancer Institute Referral Office
- Numero di telefono: 888-624-1937
- Email: NCIMO_Referrals@mail.nih.gov
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
- Adulto
- Adulto più anziano
Accetta volontari sani
Descrizione
- INCLUSION CRITERIA:
- Participants must have a histologically or cytologically confirmed by pathology report diagnosis of colorectal cancer (CRC), intrahepatic cholangiocarcinoma (ICC), or adrenocortical carcinoma (ACC).
- Participants must have measurable liver-dominant metastatic disease. Note: liver-dominant metastatic disease is defined as >=75% of metastatic disease present in the liver as assessed by the principal investigator.
- Extrahepatic disease should be treated with anticancer therapy, if applicable, and should be stable by RECIST criteria for at least 6 weeks prior to study treatment initiation.
- Participants must have previously undergone hepatic artery infusion pump therapy and have a functioning hepatic artery infusion pump in place.
- Participants must have progressed on, been intolerant of, or have residual disease after HAI floxuridine and appropriate current standard-of-care treatment.
- Age >= 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status <= 2.
- Participants must have an adequate organ and marrow function as defined below:
Leukocytes > 3,000/mcL
Hemoglobin >= 9 mg/dL
Absolute neutrophil count > 1,500/mcL
Platelets > 100,000/mcL
Total bilirubin < 2 X institutional upper limit of normal (ULN)
Aspartate aminotransferase (AST) < 2.5 X institutional (ULN)
Alanine aminotransferase (ALT) < 2.5 X institutional (ULN)
Creatinine <2 X institutional (ULN)
- Participants positive for human immunodeficiency virus (HIV) 1/2 antibody must have a negative HIV viral load.
- Participants positive for Hepatitis C (HCV) antibody must have a negative HCV viral load.
- Participants positive for Hepatitis B (HBV) core antibody (HBcAb) must have a negative HBV viral load. Note: Participants positive for Hepatitis B surface antigen (HBsAg) are excluded.
- Women of childbearing potential (WOCBP) must agree to use effective contraception (barrier, hormonal, intrauterine device, abstinence, surgical sterilization) at the study entry and up to 6 months after the last dose of the study drug. A participant may request a male partner to use an effective form of contraception to fulfill this requirement (e.g., condom/barrier).
Men must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) at the study entry and up to 3 months after the last dose of the study drug. A participant may request a female partner to use an effective form of contraception to fulfill this requirement (e.g., intrauterine device, hormonal contraceptives). Men must not freeze or donate sperm within the same period.
- Women who are breastfeeding or plan to breastfeed must agree to discontinue/postpone breastfeeding from study treatment initiation through 2 weeks after the last dose of the study drug.
- Ability of participant to understand and the willingness to sign a written informed consent document.
EXCLUSION CRITERIA:
- Participants with liver metastases amenable to resection.
- Participants who received floxuridine within 6 weeks prior to the study treatment initiation.
- Participants who received any anticancer therapy within 2 weeks prior to the study treatment initiation.
- Participants who received any investigational agents within 4 weeks prior to the study treatment initiation.
- Participants with incontrovertible radiographic evidence of disease progression per the RECIST definition outside of the liver within 3 months prior to the study treatment initiation. Note: Pulmonary lesions less than 1 cm are allowed.
- Prior radiation to the liver (Yttrium-90 [Y-90] or External Beam Radiation Therapy [EBRT]).
- History of allergic reactions attributed to compounds of similar chemical composition to CFZ.
- Positive serum or urine Beta-human chorionic gonadotropin (Beta-HCG) pregnancy test performed at screening.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, evaluated by medical history, electrocardiogram (EKG), physical exam, and laboratory testing, or social situations that would unacceptably increase risk for the participant or impair the ability to evaluate the endpoints of the study or that would limit compliance with study requirements.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: N / A
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Sperimentale: 1/Phase I
Participants with liver metastatic disease will receive continuous administration of carfilzomib via Hepatic Artery Infusion Pump (HAIP)
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Variable doses, continuously administered via Hepatic Artery Infusion Pump (HAIP) for up to 6 cycles
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Establish the safety of hepatic artery infusion (HAI) of carfilzomib (CFZ) in participants with liver metastatic disease who were previously treated with HAI pump therapy
Lasso di tempo: DLT assessment will occur during Cycle 1 (28 days total).Assessment of adverse events will occur from the first study intervention through 28 days after the last study intervention or initiation of a new anti-cancer treatment whichever comes first
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The safety of the study therapy will be evaluated by the maximum dosage at which no more than 1 of 6 participants experience DLT during DLT period (Cycle 1) and by reporting the grade and type of toxicity at each dose level
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DLT assessment will occur during Cycle 1 (28 days total).Assessment of adverse events will occur from the first study intervention through 28 days after the last study intervention or initiation of a new anti-cancer treatment whichever comes first
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Establish the Overall Response Rate (ORR), defined as complete response (CR) + partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST)
Lasso di tempo: Assessed based on imaging studies prior to starting cycles 1, 3 and 5, Day 28 Safety visit, and 3-month Follow Up visit
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The proportion of participants with partial response or complete response along with a 95% confidence interval (analyzed in a combined fashion, regardless of dose level).
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Assessed based on imaging studies prior to starting cycles 1, 3 and 5, Day 28 Safety visit, and 3-month Follow Up visit
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Collaboratori e investigatori
Sponsor
Investigatori
- Investigatore principale: Jonathan M Hernandez, M.D., National Cancer Institute (NCI)
Pubblicazioni e link utili
Pubblicazioni generali
- Larrain CM, Victory JH, Desai PP, Friedman LR, Stepp H, Ashe R, Remmert K, Sinha S, Smith EC, Russell N, Pu T, Eade AV, Burke JF, Ho J, Yaffe MB, Kleiner DE, Schmidt K, Figg WD, Hernandez JM. A rebrand for proteasome inhibition in solid tumors via continuous hepatic artery infusion. JCI Insight. 2025 Nov 4;10(24):e199200. doi: 10.1172/jci.insight.199200. eCollection 2025 Dec 22.
- Jun Y, Xu J, Kim H, Park JE, Jeong YS, Min JS, Yoon N, Choi JY, Yoo J, Bae SK, Chung SJ, Yeo Y, Lee W. Carfilzomib Delivery by Quinic Acid-Conjugated Nanoparticles: Discrepancy Between Tumoral Drug Accumulation and Anticancer Efficacy in a Murine 4T1 Orthotopic Breast Cancer Model. J Pharm Sci. 2020 Apr;109(4):1615-1622. doi: 10.1016/j.xphs.2020.01.008. Epub 2020 Jan 13.
- Zeng TM, Jiang TY, Yang G, Cheng Z, Lou C, Wei W, Tao CJ, Hu S, Wang H, Cui XW, Tan YX, Dong LW, Wang HY, Yuan ZG. Bortezomib in previously treated phosphatase and tension homology-deficient patients with advanced intrahepatic cholangiocarcinoma: An open-label, prospective and single-centre phase II trial. Clin Transl Med. 2024 May;14(5):e1675. doi: 10.1002/ctm2.1675.
- Tilk S, Frydman J, Curtis C, Petrov DA. Cancers adapt to their mutational load by buffering protein misfolding stress. Elife. 2024 Nov 25;12:RP87301. doi: 10.7554/eLife.87301.
Collegamenti utili
Studiare le date dei record
Studia le date principali
Inizio studio (Stimato)
Completamento primario (Stimato)
Completamento dello studio (Stimato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie del sistema endocrino
- Processi patologici
- Neoplasie per sede
- Malattie intestinali
- Neoplasie per tipo istologico
- Neoplasie gastrointestinali
- Neoplasie dell'apparato digerente
- Malattie dell'apparato digerente
- Malattie gastrointestinali
- Neoplasie intestinali
- Malattie del retto
- Neoplasie delle ghiandole endocrine
- Neoplasie, ghiandolari ed epiteliali
- Adenocarcinoma
- Malattie del colon
- Processi neoplastici
- Carcinoma
- Neoplasie della ghiandola surrenale
- Malattie della corteccia surrenale
- Malattie della ghiandola surrenale
- Condizioni patologiche, segni e sintomi
- Neoplasie
- Neoplasie colorettali
- Metastasi neoplastica
- Colangiocarcinoma
- Carcinoma surrenalico
- Neoplasie della corteccia surrenale
- carfilzomib
Altri numeri di identificazione dello studio
- 10002574
- 002574-C
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Descrizione del piano IPD
Periodo di condivisione IPD
Criteri di accesso alla condivisione IPD
Tipo di informazioni di supporto alla condivisione IPD
- STUDIO_PROTOCOLLO
- LINFA
- ICF
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
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