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

NCT04552093 | Unknown Phase 2 DMC

• 3 other identifiers: M19PITNL70112.031.192019-003260-44
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Neoplasms

Keywords

Hepatic artery infusion pump; Colorectal liver metastases; FUDR; Floxuridine; CRLM

Outcome Measures

Primary Outcomes (1)

• Completion of 2 combined chemotherapy cycles (feasibility)

  The percentage of patients that complete two cycles of combined chemotherapy (HAIP chemotherapy and systemic therapy) after being scheduled for surgical implantation.

  Approximately 4 months after patient inclusion

Secondary Outcomes (7)

• Safety: Postoperative complications

  90 days after surgery

• Safety: Drug treatment toxicity

  1.5 year

• Safety: Other adverse events

  1.5 year

• Response rate colorectal liver metastases (CRLM)

  8 months after patient registration

• Progression free survival (PFS)

  1.5 year

Other Outcomes (1)

• Quality of life assessment

  8 months after patient inclusion

Study Arms (1)

Colorectal liver metastases

EXPERIMENTAL

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; Device: Tricumed IP2000V infusion pump

Interventions

Floxuridine DRUG

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).

Also known as: FUDR

Colorectal liver metastases

Tricumed IP2000V infusion pump DEVICE

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

Colorectal liver metastases

Eligibility Criteria

• Age: 18 Years - 115 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Erasmus Medical Center: collaborator

Study Sites (1)

Antoni van Leeuwenhoek (NKI-AVL)

Amsterdam, 1066 CX, Netherlands

RECRUITING

Related Publications (1)

• Krul MF, Kok NFM, Osmani H, Buisman FE, Groot Koerkamp B, Grunhagen DJ, Verhoef C, Mostert B, Snaebjornsson P, Westerink B, Klompenhouwer EG, Donswijk ML, Ruers TJM, Douma JAJ, van Blijderveen N, Kingham TP, D'Angelica MI, Kemeny NE, Bolhuis K, Buffart TE, Kuhlmann KFD. Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy for borderline resectable and unresectable colorectal liver metastases: phase II feasibility study. Br J Surg. 2024 Apr 3;111(4):znae089. doi: 10.1093/bjs/znae089.

  PMID: 38608150 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Floxuridine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxyuridine; Uridine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Koert FD Kuhlmann, MD, PhD

  Antoni van Leeuwenhoek

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Myrtle F Krul, MD

CONTACT

+31205129111; pump@nki.nl

Roos Steenhuis, MSc

CONTACT

+31205129111

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: September 10, 2020
• First Posted: September 17, 2020
• Study Start: September 9, 2020
• Primary Completion: June 30, 2022
• Study Completion: December 31, 2022
• Last Updated: September 17, 2020

Record last verified: 2020-09

Locations

NL (1)