High risk locally advanced rectal cancer
Conditions
Interventions
Trade Name: Oxaliplatin
Pharmaceutical Form: Infusion
Trade Name: 5-fluorouracil
Pharmaceutical Form: Infusion
Trade Name: Leucovorin
Pharmaceutical Form: Infusion
Trade Name: Irinotecan
Pharmaceut
Sponsors
Catharina Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - 18 years or older - Histopathologically confirmed rectal cancer. - Confirmed high-risk locally advanced rectal cancer, meeting the following imaging based criteria: o Tumour invasion of mesorectal fascia (MRF) o The presence of grade 4 extramural venous invasion (mrEMVI) o The presence of tumour deposits o The presence of Extramesorectal lymph nodes with a short-axis size > 7mm - Resectable disease as determined on magnetic resonance imaging (MRI) or deemed resectable disease after neoadjuvant treatment. Expected gross incomplete resection with overt tumour remaining in the patient after resection, tumour invasion in the neuroforamina, encasement of the ischiadic nerve and invasion of the cortex from S3 and upwards are considered not resectable - WHO performance score 0-1 - Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 38
Exclusion criteria
Exclusion criteria: - Evidence of metastatic disease at the moment of randomisation or within six months prior to randomisation except for patients with enlarged iliac or inguinal lymph nodes and aspecific lung noduli. - Homozygous DPD deficiency - Any chemotherapy within the past 6 months - Any contraindication for the planned chemotherapy (e.g. severe allergy, pregnancy, kidney dysfunction and thrombocytopenia), as determined by the medical oncologist. - Radiotherapy in the pelvic area within the past 6 months. - 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. - Any contraindication to undergo surgery, as determined by the surgeon and/or anaesthesiologist. - Concurrent malignancies that interfere with the planned study treatment or the prognosis of the resected tumour.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate if the addition of induction therapy 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. ;Secondary Objective: To determine: • the recurrence free survival. • the distant metastasis free survival. • the progression free survival. • the disease free survival. • the overall survival. • the radiological response after induction therapy. • the radiological response after induction therapy and chemoradiotherapy. • the pathological response. • the toxicity related to the administration of induction therapy. • the compliance related to the administration of induction therapy. • the toxicity related to the administration of chemoradiotherapy. • the compliance related to the administration of chemoradiotherapy. • the number of patients undergoing surgery. • the type and extent of surgery after neoadjuvant therapy. • the major surgical complications rate. • the quality of life. • the cost-effectiveness and –utility. •To systemically collect blood and tissue samples for future translational research. ;Primary end point(s): The proportion of patients with a pathological complete response (pCR) and those patients who started a wait and see strategy and have sustained clinical complete response (cCR) at 1 year after ICT + CRT.;Timepoint(s) of evaluation of this end point: After postoperative histopathological evaluation and 1 year after ICT + CRT | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Local recurrence free survival: at 3-year and 5-year follow-up. • Distant metastasis free survival: at 3-year and 5-year follow-up. • Progression free survival: at 3-year and 5-year follow-up. • Disease free survival: at 3-year and 5-year follow-up. • Overall survival: at 3-year and 5-year follow-up. • Radiological response after induction chemotherapy: after restaging MRI/CT before chemoradiotherapy/consolidation chemotherapy. • Radiological response after chemoradiotherapy: after restaging MRI/CT. • Pathologic response. after histopathological evaluation. • Toxicity related to induction chemotherapy: 1 month after finishing induction chemotherapy. • The induction chemotherapy compliance rate: after restaging. • Toxicity of chemoradiotherapy: 1 month after finishing chemoradiotherapy. • The compliance rate related to chemoradiotherapy: after restaging. • Number of patients undergoing surgery: after determining whether the last patients proceeds to surgery or not. • Type and extent of surgery: directly after surgery. • Major surgical morbidity rate: after 90 days postoperatively. • Quality of life: at inclusion and 3 and 12 months postoperatively. • Cost-effectiveness: at inclusion and 3 and 12 months postoperatively. ;Timepoint(s) of evaluation of this end point: See E5.2 | — |
Countries
Netherlands
Contacts
Public ContactKim van den Berg
Catharina Hospital
Outcome results
None listed