Clinical trial NCT06003998: Intraperitoneal Irinotecan With Concomitant FOLFOX and Bevacizumab
Official title: Intraperitoneal Irinotecan With Concomitant FOLFOX and Bevacizumab for Patients With Unresectable Colorectal Peritoneal Metastases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Colorectal Cancer
Peritoneal Metastases
Keywords: Peritoneal metastases
colorectal cancer
Intraperitoneal
Irinotecan
Lead sponsor: Catharina Ziekenhuis Eindhoven
Sponsor class: OTHER
First posted: 2023-08-22
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The rationale of the current study is that the addition of intraperitoneal irinotecan (75 mg) to palliative systemic therapy is feasible and safe, and might result in an increased overall and progression free survival in patients with unresectable colorectal peritoneal metastases. The primary objectives are to explore the overall survival for the addition of intraperitoneal irinotecan (75 mg) to palliative systemic therapy in patients with unresectable colorectal peritoneal metastases. Secondary objectives are to assess the progression-free survival, toxicity profile, patient reported outcomes, costs, tumor response during trial treatment, and the systemic and intraperitoneal pharmacokinetics of irinotecan and SN-38. This is a single-arm, open-label, phase II study and patients will receive intraperitoneal irinotecan (75 mg) in combination with modified FOLFOX4 + bevacizumab.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed colorectal cancer;
* Radiologically and clinically or pathologically confirmed unresectable colorectal peritoneal metastases (e.g. PCI \>20, extensive small bowel involvement, unresectable disease due to anatomical location);
* WHO performance score of 0-1 with a life expectancy of \>3 months;
* Aged 18 years or older;
* Written informed consent;

Exclusion Criteria:

* Presence of extensive systemic metastases that are deemed to be the dominant factor determining prognosis in terms of life expectancy and performance status \[e.g. no imminent threat of impaired organ functioning due to the presence of systemic metastases\]);
* Prior cytoreductive surgery;
* Prior palliative systemic therapy for colorectal cancer;
* Prior neo-adjuvant/adjuvant systemic therapy for colorectal cancer within the last 6 months;
* Homozygous UGT1A1\*28 genotype;
* Homozygous dihydropyrimidine dehydrogenase (DPD) deficiency
* Microsatellite instable (MSI) primary tumor
* Any contra-indication for the planned chemotherapy (e.g. active infection, serious concomitant disease, severe allergy), as determined by the medical oncologist;
* Inadequate organ functions, defined as an haemoglobin of \<5 mmol/L, an absolute neutrophil count of \<1.5 x 109/L, platelet count of \<100 x 109/L, serum creatinine of \>1.5 x ULN, creatinine clearance of \<30 ml/min, Bilirubin \> 2x ULN and liver transaminases of \>5 x ULN.

Primary outcomes:
measure: Overall survival
timeFrame: 3 year
Secondary outcomes:
measure: Progression-free survival
timeFrame: 3 year
measure: Toxicity in CTCAE grading
timeFrame: 28 weeks. Each cycle is 2 weeks, maximum of 12 cycles. Toxicity measured up to four weeks after last cycle.
measure: Patient-reported outcomes (PROs) with EQ-5D-5L
timeFrame: 24 weeks. Each cycle is 2 weeks, maximum of 12 cycles. Measured one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle.
measure: Patient-reported outcomes (PROs) with EORTC QLQ-C30
timeFrame: 24 weeks. Each cycle is 2 weeks, maximum of 12 cycles. Measured one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle.
measure: Patient-reported outcomes (PROs) with EORTC QLQ-CR29
timeFrame: 24 weeks. Each cycle is 2 weeks, maximum of 12 cycles. Measured one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle.
measure: Healthcare costs
timeFrame: 24 weeks. Each cycle is 2 weeks, maximum of 12 cycles. Measured one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle.
measure: Productivity loss costs.
timeFrame: 24 weeks. Each cycle is 2 weeks, maximum of 12 cycles. Measured one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle.
measure: Occurrence and degree of nephrotoxicity
timeFrame: 24 weeks. Each cycle is 2 weeks, maximum of 12 cycles.
measure: Occurrence and degree of hepatotoxicity
timeFrame: 24 weeks. Each cycle is 2 weeks, maximum of 12 cycles.
measure: Occurrence and degree of haematological toxicity
timeFrame: 24 weeks. Each cycle is 2 weeks, maximum of 12 cycles.
measure: Response of Tumor marker during treatment
timeFrame: 24 weeks. Each cycle is 2 weeks, maximum of 12 cycles.
measure: Number of patients that completed twelve cycles
timeFrame: 24 weeks. Each cycle is 2 weeks, maximum of 12 cycles.
measure: Objective radiological response
timeFrame: 24 weeks. Each cycle is 2 weeks, maximum of 12 cycles. Measured at baseline, after the fourth cycle, after the eighth cycle, and after the twelfth cycle.
measure: Peritoneum/plasma ratio of intraperitoneal irinotecan
timeFrame: 8 weeks. Each cycles is 2 weeks. Measured during cycle 1 and cycle 4.
Other outcomes:
Locations:
city: Eindhoven
country: Netherlands
facility: Catharina Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Centre
Study officials:
References: