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Hepatic Arterial Infusion Pump Chemotherapy Combined With Systemic Chemotherapy (PUMP-IT) (PUMP-IT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04552093
Recruitment Status : Recruiting
First Posted : September 17, 2020
Last Update Posted : September 17, 2020
Sponsor:
Collaborator:
Erasmus Medical Center
Information provided by (Responsible Party):
The Netherlands Cancer Institute

Brief Summary:
The PUMP-IT study is designed to prove the feasibility of HAIP chemotherapy with concomitant standard systemic chemotherapy (FOLFOX and FOLFIRI) in the Netherlands. This study will include patients with both unresectable CRLM and resectable CRLM with an indication for upfront systemic therapy (further referred to as potentially resectable CRLM), without extrahepatic metastases. The study will be performed in two tertiary referral centers in the Netherlands.

Condition or disease Intervention/treatment Phase
Colorectal Neoplasms Drug: Floxuridine Device: Tricumed IP2000V infusion pump Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 31 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Patients with potentially resectable (i.e. unresectable or upfront resectable with an indication for upfront systemic therapy) will receive hepatic artery infusion pump chemotherapy, consisting of floxuridine (FUDR), combined with standard of care systemic therapy (FOLFOX or FOLFIRI).
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Hepatic Arterial Infusion PUMP Chemotherapy Combined With systemIc chemoTherapy for Potentially Resectable Colorectal Liver Metastases: The PUMP-IT Study.
Actual Study Start Date : September 9, 2020
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Floxuridine

Arm Intervention/treatment
Experimental: Colorectal liver metastases
Patients with potentially resectable colorectal liver metastases will undergo hepatic artery infusion pump placement. Subsequent hepatic artery infusion of floxuridine via the HAIP as well as standard of care Dutch systemic chemotherapy (FOLFOX or FOLRIRI) will be administered in a combined chemotherapy schedule.
Drug: Floxuridine
Administration of intra-arterial floxuridine via the HAIP (HAIP chemotherapy) to the liver with concomitant Dutch standard of care systemic FOLFOX (5-FU, leucovorin and oxaliplatin) or FOLFIRI (5-FU, leucovorin and irinotecan).
Other Name: FUDR

Device: Tricumed IP2000V infusion pump
Surgical implantation of hepatic artery infusion pump (HAIP) followed by administration of the combined chemotherapy (HAIP and systemic).




Primary Outcome Measures :
  1. Completion of 2 combined chemotherapy cycles (feasibility) [ Time Frame: Approximately 4 months after patient inclusion ]
    The percentage of patients that complete two cycles of combined chemotherapy (HAIP chemotherapy and systemic therapy) after being scheduled for surgical implantation.


Secondary Outcome Measures :
  1. Safety: Postoperative complications [ Time Frame: 90 days after surgery ]
    Surgical complications will be defined according to Clavien-Dindo surgical complications score. Complications of Clavien-Dindo grade 3 or higher are recorded for the first 90 days after surgery. Postoperative complications include those related to the HAIP implantation. Postoperative mortality is defined as any death during hospitalization or within 90 days from surgery.

  2. Safety: Drug treatment toxicity [ Time Frame: 1.5 year ]
    Toxicity grade 3 or higher will be recorded from the time of study inclusion according to the CTCAE criteria.

  3. Safety: Other adverse events [ Time Frame: 1.5 year ]
    Treatment related serious adverse events (SAE) and adverse events (AE) of grade 3 or higher will be collected continuously from the time of study inclusion until the end of combined chemotherapy. AE are followed up until the event is either resolved or adequately explained, even after the patient has completed his/her study treatment. Nature and duration of any hospitalization, treatment of any AE, and nature and duration of any outpatient care will be recorded.

  4. Response rate colorectal liver metastases (CRLM) [ Time Frame: 8 months after patient registration ]
    Response rates of CRLM will be measured according to RECIST criteria

  5. Progression free survival (PFS) [ Time Frame: 1.5 year ]
    PFS will be defined from inclusion date until disease progression.

  6. Overall survival (OS) [ Time Frame: 1.5 year ]
    OS will be defined from inclusion date until death.

  7. Conversion rate colorectal liver metastases (CRLM) [ Time Frame: 8 months after patient inclusion ]
    Conversion rate is defined as the percentage of patients in whom CRLM convert from an unresectable to a resectable state and undergo surgical treatment with curative intent. Possibility of local treatment is at the discretion of the multidisciplinary liver panel.


Other Outcome Measures:
  1. Quality of life assessment [ Time Frame: 8 months after patient inclusion ]
    The quality of life will be examined with validated questionnaires (EORTC QLQ-C30 & EQ-5D-3L).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 115 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age ≥ 18 years.
  • ECOG performance status 0 or 1.
  • Life expectancy of at least 12 weeks.
  • Histologically confirmed CRC.
  • Indication for first or second line systemic therapy, confirmed in a multidisciplinary meeting.
  • Potentially resectable (i.e. unresectable and upfront resectable CRLM with indication for neoadjuvant systemic therapy), confirmed in a multidisciplinary meeting and radio-logically on (PET) CT thorax/abdomen and/or MRI obtained ≤ 4 weeks prior to regis-tration.
  • Positioning of a catheter for HAIP chemotherapy is technically feasible confirmed in the multidisciplinary liver meeting based on imaging. The default site for the catheter insertion is the gastroduodenal artery (GDA). Accessory or aberrant hepatic arteries are no contra-indication for catheter implantation. The GDA should have at least one branch to the liver, accessory or aberrant hepatic arteries should be ligated to allow for cross perfusion to the entire liver through intrahepatic shunts.
  • Indication and eligibility for abdominal surgery confirmed in a multidisciplinary meeting, e.g. primary tumour resection, stoma revision/reversal and diagnostic surgery.
  • In case of primary tumour in situ: tumour should be (potentially) resectable, confirmed in a multidisciplinary meeting.
  • Adequate bone marrow, liver and renal function as assessed by the following labora-tory requirements to be conducted within 15 days prior to inclusion.

    • Hb ≥ 5.5 mmol/L
    • Absolute neutrophil count (ANC) ≥1.5 * 109/L
    • Platelets ≥100 * 109/L
    • Total bilirubin < 1.5 mg/dL
    • ASAT ≤ 5 * times the upper limit of normal (ULN)
    • ALAT ≤ 5 * ULN
    • Alkaline phosphatase ≤ 5 * ULN
    • (estimated) glomerular filtration rate (eGFR) > 45 ml/min.
  • Before patient registration, written informed consent must be given and signed according to ICH-GCP, and national/local regulations.

Exclusion Criteria:

  • Extrahepatic metastases. Confirmed with CT thorax/abdomen obtained ≤ 4 weeks prior to registration. Patients with small (≤ 1 cm) extrahepatic lesions that are not clearly suspicious of metastases are eligible.
  • Prior hepatic radiation, resection (other than biopsy), or ablation.
  • Concurrent malignancies that interfere with the planned study treatment or the prognosis of CRLM.
  • Participation in other clinical trials interfering with the study treatment as judged by the treating physician.
  • Dihydropyrimidine dehydrogenasedeficiency (DPD deficiency).
  • Pregnant or lactating women.
  • Serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator.
  • Organ allografts requiring immunosuppressive therapy.
  • Serious, non-healing wound, ulcer, or bone fracture.
  • Chronic treatment with corticosteroids (dose of ≥ 10 mg/day methylprednisolone equiv-alent excluding inhaled steroids).
  • Serious infections (uncontrolled or requiring treatment).
  • History of psychiatric disability judged by the investigator to potentially hamper compliance with the study protocol and follow-up schedule.
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04552093


Contacts
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Contact: Myrtle F Krul, MD +31205129111 pump@nki.nl
Contact: Roos Steenhuis, MSc +31205129111

Locations
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Netherlands
Antoni van Leeuwenhoek (NKI-AVL) Recruiting
Amsterdam, Netherlands, 1066 CX
Principal Investigator: Koert FD Kuhlmann, MD, PhD         
Sponsors and Collaborators
The Netherlands Cancer Institute
Erasmus Medical Center
Investigators
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Principal Investigator: Koert FD Kuhlmann, MD, PhD Antoni van Leeuwenhoek
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Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT04552093    
Other Study ID Numbers: M19PIT
NL70112.031.19 ( Registry Identifier: Registry ID: CCMO )
2019-003260-44 ( EudraCT Number )
First Posted: September 17, 2020    Key Record Dates
Last Update Posted: September 17, 2020
Last Verified: September 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by The Netherlands Cancer Institute:
Hepatic artery infusion pump
Colorectal liver metastases
FUDR
Floxuridine
CRLM
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Floxuridine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents