Intraperitoneal Irinotecan With Concomitant FOLFOX and Bevacizumab

NCT06003998 | Unknown Phase 2

• 1 other identifier: NL81672.100.22
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 2

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

Keywords

Peritoneal metastases; colorectal cancer; Intraperitoneal; Irinotecan

Outcome Measures

Primary Outcomes (1)

• Overall survival

  calculated from (a) the interval from diagnosis of peritoneal metastases until death or last follow-up; (b) the interval from the first day of the first cycle until death or last follow-up).

  3 year

Secondary Outcomes (14)

• Progression-free survival

  3 year

• Toxicity in CTCAE grading

  28 weeks. Each cycle is 2 weeks, maximum of 12 cycles. Toxicity measured up to four weeks after last cycle.

• Patient-reported outcomes (PROs) with EQ-5D-5L

  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.

• Patient-reported outcomes (PROs) with EORTC QLQ-C30

  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.

• Patient-reported outcomes (PROs) with EORTC QLQ-CR29

  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.

Study Arms (1)

Intraperitoneal irinotecan 75 mg + mFOLFOX-4 and bevacizumab

EXPERIMENTAL

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

Drug: Irinotecan; Drug: FOLFOX regimen; Drug: Bevacizumab

Interventions

Irinotecan DRUG

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

Also known as: Intraperitoneal irinotecan

Intraperitoneal irinotecan 75 mg + mFOLFOX-4 and bevacizumab

FOLFOX regimen 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

Also known as: 5-FU + oxaliplatin

Intraperitoneal irinotecan 75 mg + mFOLFOX-4 and bevacizumab

Bevacizumab DRUG

Bevacizumab according to standard of care

Also known as: Avastin

Intraperitoneal irinotecan 75 mg + mFOLFOX-4 and bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Catharina Ziekenhuis Eindhoven: lead

Study Sites (2)

Catharina Hospital

Eindhoven, Netherlands

RECRUITING

Erasmus Medical Centre

Rotterdam, Netherlands

RECRUITING

Related Publications (1)

• 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.

  PMID: 38238055 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Irinotecan; Folfox protocol; Fluorouracil; Oxaliplatin; Bevacizumab

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)

Camptothecin; Alkaloids; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Pim Burger, MD, PhD

CONTACT

0031402397150; pim.burger@catharinaziekenhuis.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 8, 2022
• First Posted: August 22, 2023
• Study Start: December 27, 2022
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: August 22, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2)