eo-adjuvant FOLFOXIRI and chemoradiotherapy for high risk (*ugly*) locally advanced rectal cancer.

Phase 2

Recruiting

• Conditions: High risk locally advanced rectal cancer; rectal cancer of a locally advanced stage; 10017991; 10017998

• Registration Number: NL-OMON52634
• Lead Sponsor: Catharina-ziekenhuis

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 128

Inclusion Criteria

• 18 years or older
• WHO performance score 0-1.
• Fit for (modified dose) triple chemotherapy (FOLFOXIRI)
• Histopathologically confirmed rectal cancer.
• Lower border of the tumour located on or below the sigmoidal take-off as
established on MRI of the pelvis.
• Confirmed high-risk locally advanced rectal cancer, at high risk of treatment
failure, meeting one of 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 (TD)
o 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.
• 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 S2 and upwards are considered
not resectable
• Written informed consent.

Exclusion Criteria

• 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 noduli.
• Homozygous DPD deficiency.
• Any chemotherapy within the past 6 months.
• Any contraindication for the planned systemic therapy (e.g. severe allergy,
pregnancy, kidney dysfunction and thrombocytopenia), as determined by the
medical oncologist.
• Previous radiotherapy in the pelvic area precluding chemoradiotherapy with a
dose of 50 - 50.4 Gy.
• 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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint of this study is the number of patients with a complete<br /><br>pathological response or sustained clinical complete response (1 year) after<br /><br>ICT+CRT.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints are clinical response to ICT and ICT+CRT, pathological<br /><br>response, R0 resection rate, local recurrence free survival, distant metastases<br /><br>free survival, progression free survival, disease free survival and overall<br /><br>survival, systemic therapy related toxicity (NCI-CTCAE v5.0 grade >=3),<br /><br>completion of neoadjuvant treatment, major postoperative complications<br /><br>(Clavien-Dindo grade >=3, up to 30 days postoperatively), quality of life and<br /><br>costs.</p><br>