Intraperitoneal Irinotecan With Concomitant FOLFOX and Bevacizumab

NCT ID: NCT06003998

Last Updated: 2023-08-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 85 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-27
• Study Completion Date: 2025-01-01

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.

Conditions

Colorectal Cancer; Peritoneal Metastases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intraperitoneal irinotecan 75 mg + mFOLFOX-4 and bevacizumab

Intraperitoneal irinotecan, 75 mg flat dose + systemic oxaliplatin, 5-Fluorouracil and bevacizumab (mFOLFOX+beva) (dose via standard of care)

Group Type: EXPERIMENTAL

Irinotecan

Intervention Type: DRUG

2 weekly IP irinotecan (max 12 cycles), dose 75 mg flat dose

FOLFOX regimen

Intervention Type: DRUG

FOLFOX-4 regimens consist of 85 mg/m2 oxaliplatin plus 200 mg/m2 LV and 5-FU 400 mg/m2 bolus on day 1 followed by 1600 mg/m2 5-FU as a 46-h infusion

Bevacizumab

Intervention Type: DRUG

Bevacizumab according to standard of care

Interventions

Irinotecan

2 weekly IP irinotecan (max 12 cycles), dose 75 mg flat dose

Intervention Type: DRUG

FOLFOX regimen

FOLFOX-4 regimens consist of 85 mg/m2 oxaliplatin plus 200 mg/m2 LV and 5-FU 400 mg/m2 bolus on day 1 followed by 1600 mg/m2 5-FU as a 46-h infusion

Intervention Type: DRUG

Bevacizumab

Bevacizumab according to standard of care

Intervention Type: DRUG

Other Intervention Names

Intraperitoneal irinotecan; 5-FU + oxaliplatin; Avastin

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Catharina Ziekenhuis Eindhoven

OTHER

Sponsor Role: lead

Responsible Party

J. W. A. Burger

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Catharina Hospital

Eindhoven, , Netherlands

Site Status: RECRUITING

Erasmus Medical Centre

Rotterdam, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Pim Burger, MD, PhD

Role: CONTACT

pim.burger@catharinaziekenhuis.nl

0031402397150

Facility Contacts

Teun van den Heuvel, MD

Role: primary

teun.vd.heuvel@catharinaziekenhuis.nl

0031 40 239 6351

Niels Guchelaar

Role: primary

n.guchelaar@erasmusmc.nl

0031 10 703 9640

References

van de Vlasakker VCJ, Guchelaar NAD, van den Heuvel TBM, Lurvink RJ, van Meerten E, Bax RJF, Creemers GM, van Hellemond IEG, Brandt-Kerkhof ARM, Madsen EVE, Nederend J, Koolen SLW, Nienhuijs SW, Kranenburg O, de Hingh IHJT, Verhoef C, Mathijssen RHJ, Burger JWA; Dutch Peritoneal Oncology Group; Dutch Colorectal Cancer Group. Intraperitoneal irinotecan with concomitant FOLFOX and bevacizumab for patients with unresectable colorectal peritoneal metastases: protocol of the multicentre, open-label, phase II, INTERACT-II trial. BMJ Open. 2024 Jan 18;14(1):e077667. doi: 10.1136/bmjopen-2023-077667.

Reference Type: DERIVED

PMID: 38238055 (View on PubMed)

Other Identifiers

NL81672.100.22

Identifier Type: -

Identifier Source: org_study_id