- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning 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.
...
Studieöversikt
Status
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Inskrivning (Beräknad)
Fas
- Fas 1
Kontakter och platser
Studiekontakt
- Namn: Kathleen M Smith, R.N.
- Telefonnummer: (240) 858-3531
- E-post: kathleen.smith3@nih.gov
Studera Kontakt Backup
- Namn: Jonathan M Hernandez, M.D.
- Telefonnummer: (240) 760-6072
- E-post: jonathan.hernandez@nih.gov
Studieorter
-
-
Maryland
-
Bethesda, Maryland, Förenta staterna, 20892
- National Institutes of Health Clinical Center
-
Kontakt:
- National Cancer Institute Referral Office
- Telefonnummer: 888-624-1937
- E-post: ncimo_referrals@mail.nih.gov
-
-
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
- 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.
Studieplan
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: 1/Phase I
Participants with liver metastatic disease will receive continuous administration of carfilzomib via Hepatic Artery Infusion Pump (HAIP) |
Variable doses, continuously administered via Hepatic Artery Infusion Pump (HAIP) for up to 6 cycles |
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
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
Tidsram: 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
|
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 |
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
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Establish the Overall Response Rate (ORR), defined as complete response (CR) + partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST)
Tidsram: Assessed based on imaging studies prior to starting cycles 1, 3 and 5, Day 28 Safety visit, and 3-month Follow Up visit
|
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). |
Assessed based on imaging studies prior to starting cycles 1, 3 and 5, Day 28 Safety visit, and 3-month Follow Up visit
|
Samarbetspartners och utredare
Sponsor
Utredare
- Huvudutredare: Jonathan M Hernandez, M.D., National Cancer Institute (NCI)
Publikationer och användbara länkar
Allmänna publikationer
- 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.
Användbara länkar
Studieavstämningsdatum
Studera stora datum
Studiestart (Beräknad)
Primärt slutförande (Beräknad)
Avslutad studie (Beräknad)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Faktisk)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- Sjukdomar i det endokrina systemet
- Patologiska processer
- Neoplasmer efter plats
- Tarmsjukdomar
- Neoplasmer efter histologisk typ
- Gastrointestinala neoplasmer
- Neoplasmer i matsmältningssystemet
- Matsmältningssystemets sjukdomar
- Gastrointestinala sjukdomar
- Intestinala neoplasmer
- Rektala sjukdomar
- Neoplasmer i endokrina körtel
- Neoplasmer, körtel och epitel
- Adenocarcinom
- Kolonsjukdomar
- Neoplastiska processer
- Carcinom
- Adrenal Gland Neoplasmer
- Adrenal Cortex Sjukdomar
- Adrenal Gland Sjukdomar
- Patologiska tillstånd, tecken och symtom
- Neoplasmer
- Kolorektala neoplasmer
- Neoplasma Metastas
- Kolangiokarcinom
- Binjurebarkcarcinom
- Adrenal Cortex Neoplasmer
- carfilzomib
Andra studie-ID-nummer
- 10002574
- 002574-C
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
IPD-planbeskrivning
This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review.
Tidsram för IPD-delning
Data will be made available as soon as possible or at the time of associated publication. Data not published in a manuscript will be shared via public source once the data set completes QC.
Kriterier för IPD Sharing Access
Clinical data will be made available upon request and with the permission of the study PI.
IPD-delning som stöder informationstyp
- STUDY_PROTOCOL
- SAV
- ICF
Läkemedels- och apparatinformation, studiedokument
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