IRINOTECAN HYDROCHLORIDE TRIHYDRATE for Locally advanced rectal cancer

Inclusion criteria

• {"criterion_text":"- 18 years or older"}
• {"criterion_text":"- WHO performance score 0-1"}
• {"criterion_text":"- Fit for (modified dose) triple chemotherapy (FOLFOXIRI)"}
• {"criterion_text":"- Histopathologically confirmed rectal cancer"}
• {"criterion_text":"- Lower border of the tumour located on or below the sigmoidal take-off as established on MRI of the pelvis"}
• {"criterion_text":"- Confirmed high-risk locally advanced rectal cancer, at high risk of treatment failure, meeting one of the following imaging based criteria: *Tumour invasion of the mesorectal fascia (MRF+); *The presence of grade 4 extramural venous invasion (mrEMVI); *The presence of tumour deposits (TD); *The presence of bilateral extramesorectal lymph nodes with a short-axis size ≥ 7mm (LLN) or extensive LLN involving pelvic side wall structures, at high risk of an incomplete resection"}
• {"criterion_text":"- Resectable disease as determined on magnetic resonance imaging (MRI) or deemed resectable disease after neo-adjuvant treatment (Expected gross incomplete resection with overt tumour remaining in the patient after resection, tumour invasion in the neuroforamina, encasement of the sciatic nerve and invasion of the cortex from S2 and upwards are considered not resectable)"}
• {"criterion_text":"- Written informed consent"}

Exclusion criteria

• {"criterion_text":"- Evidence of metastatic disease at time of inclusion or within six months prior to inclusion except for patients with enlarged iliac or inguinal lymph nodes and aspecific lung nodules"}
• {"criterion_text":"- Homozygous DPD deficiency"}
• {"criterion_text":"- Any chemotherapy within the past 6 months"}
• {"criterion_text":"- Any contraindication for the planned systemic therapy (e.g. severe allergy, pregnancy, kidney dysfunction and thrombocytopenia), as determined by the medical oncologist"}
• {"criterion_text":"- Previous radiotherapy in the pelvic area precluding chemoradiotherapy with a dose of 50-50.4 Gy"}
• {"criterion_text":"- Any contraindication for the planned chemoradiotherapy (e.g. severe allergy to the chemotherapy agent or no possibility to receive radiotherapy), as determined by the medical oncologist and/or radiation oncologist"}
• {"criterion_text":"- Any contraindication to undergo surgery, as determined by the surgeon and/or anaesthesiologist"}
• {"criterion_text":"- Concurrent malignancies that interfere with the planned study treatment or the prognosis of the resected tumour"}

Primary endpoints

• {"endpoint_text":"- To evaluate if the addition of induction chemotherapy with FOLFOXIRI leads to a higher pathological complete response (pCR) rate and clinical complete response (cCR) rate at 1 year in patients with high-risk locally advanced rectal cancer compared to the currently available literature regarding high-risk locally advanced rectal cancer patients treated with (chemo)radiotherapy alone or followed by consolidation chemotherapy","definition_or_measurement_approach":"Assessment of pathological complete response (pCR) rate and clinical complete response (cCR) rate at 1 year; specific measurement definitions or procedures are not specified in the provided record."}

Secondary endpoints

• {"endpoint_text":"- To determine the recurrence free survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- To determine the distant metastasis free survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- To determine the progression-free survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- To determine the disease-free survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- To determine the overall survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- To determine the radiological response after induction chemotherapy","definition_or_measurement_approach":""}
• {"endpoint_text":"- To determine the radiological response after induction chemotherapy and chemoradiotherapy","definition_or_measurement_approach":""}
• {"endpoint_text":"- To determine the pathological response as determined by Mandard grading system","definition_or_measurement_approach":""}
• {"endpoint_text":"- To determine the toxicity related to the administration of induction chemotherapy","definition_or_measurement_approach":""}
• {"endpoint_text":"- To determine the compliance related to the administration of induction chemotherapy","definition_or_measurement_approach":""}
• {"endpoint_text":"- To determine the toxicity related to the administration of chemoradiotherapy","definition_or_measurement_approach":""}
• {"endpoint_text":"- To determine the compliance related to the administration of chemoradiotherapy","definition_or_measurement_approach":""}
• {"endpoint_text":"- To determine the number of patients undergoing surgery","definition_or_measurement_approach":""}
• {"endpoint_text":"- To determine the type and extent of surgery after neoadjuvant therapy","definition_or_measurement_approach":""}
• {"endpoint_text":"- To determine the major surgical complications rate","definition_or_measurement_approach":""}
• {"endpoint_text":"- To determine the quality of life","definition_or_measurement_approach":""}
• {"endpoint_text":"- To determine the cost-effectiveness and -utility","definition_or_measurement_approach":""}
• {"endpoint_text":"- To systematically collect blood and tissue samples for future translational research","definition_or_measurement_approach":""}

Netherlands

Earliest CTIS Part Ii Submission Date

21-11-2023

Latest Decision Or Authorization Date

25-03-2024

Processing Time Days

125

Number Of Sites

20

Number Of Participants

128

Primary sponsor

Full Name

Catharina Ziekenhuis Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"Netherlands","full_name":"IKNL","duties_or_roles":"sponsorDuties codes: 1","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Netherlands","full_name":"Netherlands Cancer Institute","duties_or_roles":"Collection of tumour tissue for translational research; sponsorDuties codes: 15, 4","organisation_type":"Laboratory/Research/Testing facility"}