Patients with potentially resectable CRLM without extrahepatic metastases with an indication for systemic therapy as induction or neoadjuvant therapy. Patients have an indication for laparotomy
Conditions
Interventions
Trade Name: FUDR
Product Name: Floxuridine
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: FLOXURIDINE
CAS Number: 50-91-9
Concentration unit: mg/ml milligram(s)/m
Sponsors
Stichting Het Nederlands Kanker Instituut-Antoni van leeuwenhoek Ziekenhuis
Eligibility
Sex/Gender
All
Inclusion 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 meet-ing, 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 laborato-ry requirements to be conducted within 15 days prior to inclusion. o Hb = 5.5 mmol/L o Absolute neutrophil count (ANC) =1.5 * 109/L o Platelets =100 * 109/L o Total bilirubin 45 ml/min. • Before patient registration, written informed consent must be given and signed accord-ing to ICH-GCP, and national/local regulations. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 31
Exclusion criteria
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 clear-ly 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 prog-nosis 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 pa-tient 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 equivalent excluding inhaled steroids). • Serious infections (uncontrolled or requiring treatment). • History of psychiatric disability judged by the investigator to potentially hamper com-pliance with the study protocol and follow-up schedule. • Any psychological, familial, sociological or geographical condition potentially hamper-ing compliance with the study protocol and follow-up schedule.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is feasibility of the HAIP chemotherapy and concomitant standard systemic chemotherapy (i.e. FOLFOX and FOLFIRI) in patients with liver limited CRC in 2 centers in the Netherlands. ;Secondary Objective: • Safety (surgical complications and chemotherapy toxicity). • Response rates. • Progression Free Survival (PFS). • Overall Survival (OS). • Conversion rates. • Quality of Life (QOL). ;Primary end point(s): The primary endpoint of this feasibility study is feasibility, presented as the percentage of in-cluded patients scheduled for surgery which can be treated with at least 2 cycles of HAIP chemotherapy combined with concomitant systemic chemotherapy. ;Timepoint(s) of evaluation of this end point: The analysis of feasibility will be conducted 3-4 months after inclusion of the last patient. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints include safety (surgical complications and drug treatment toxicity), response rates, PFS, OS and conversion rate. • Safety: Postoperative complications Surgical complications will be defined according to Clavien-Dindo surgical complica-tions score, Appendix D. Complications of Clavien-Dindo grade 3 or higher are rec-orded for the first 90 days after surgery. Postoperative complications include those re-lated to the HAIP implantation. Postoperative mortality is defined as any death during hospitalization or within 90 days from surgery. • Safety: Drug treatment toxicity Toxicity grade 3 or higher will be recorded from the time of study inclusion according to the CTCAE version 5.0, Appendix B. • Safety: Other adverse events 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. See chapter 9.2 for detailed description of the adverse events. 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. • Response rates of CRLM will be measured according to RECIST 1.1 criteria version 5.0 (Appendix E). • PFS will be defined from inclusion date until disease progression. • OS will be defined from inclusion date until death. • 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. ;Timepoint(s) of evaluation of this end point: Secondary endpoints will be assessed after HAIP chemotherapy discontinuation, approximately 6 months after the last patient started the combined | — |
Countries
Netherlands
Contacts
Public ContactDr. K.F.D. Kuhlmann
Stichting Het Nederlands Kanker Instituut-Antoni van leeuwenhoek Ziekenhuis
Outcome results
None listed