MedPath

Induction chemotherapy for locally advanced rectal cancer.

Phase 2
Active, not recruiting
Conditions
Locally advanced rectal cancer
Registration Number
2023-509758-74-00
Lead Sponsor
Catharina Ziekenhuis Stichting
Brief Summary

The primary objective of this study is 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 hr-LARC compared to the currently available literature regarding hr-LARC patients treated with (chemo)radiotherapy alone or followed by consolidation chemotherapy.

Detailed Description

Not available

Recruitment & Eligibility

Status
Ongoing, recruitment ended
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: *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

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)

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 nodules

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 clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
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

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

Secondary Outcome Measures
NameTimeMethod
To determine the quality of life

To determine the quality of life

To determine the disease-free survival

To determine the disease-free survival

To determine the overall survival

To determine the overall survival

To determine the major surgical complications rate

To determine the major surgical complications rate

To determine the progression-free survival

To determine the progression-free survival

To determine the recurrence free survival

To determine the recurrence free survival

To determine the distant metastasis free survival

To determine the distant metastasis free survival

To determine the radiological response after induction chemotherapy

To determine the radiological response after induction chemotherapy

To determine the radiological response after induction chemotherapy and chemoradiotherapy

To determine the radiological response after induction chemotherapy and chemoradiotherapy

To determine the pathological response as determined by Mandard grading system

To determine the pathological response as determined by Mandard grading system

To determine the toxicity related to the administration of induction chemotherapy

To determine the toxicity related to the administration of induction chemotherapy

To determine the compliance related to the administration of induction chemotherapy

To determine the compliance related to the administration of induction chemotherapy

To determine the toxicity related to the administration of chemoradiotherapy

To determine the toxicity related to the administration of chemoradiotherapy

To determine the compliance related to the administration of chemoradiotherapy

To determine the compliance related to the administration of chemoradiotherapy

To determine the number of patients undergoing surgery

To determine the number of patients undergoing surgery

To determine the type and extent of surgery after neoadjuvant therapy

To determine the type and extent of surgery after neoadjuvant therapy

To determine the cost-effectiveness and -utility

To determine the cost-effectiveness and -utility

To systematically collect blood and tissue samples for future translational research

To systematically collect blood and tissue samples for future translational research

Trial Locations

Locations (20)

Amsterdam UMC

🇳🇱

Amsterdam, Netherlands

Radboud universitair medisch centrum / RADBOUDUMC

🇳🇱

Nijmegen, Netherlands

Maxima Medisch Centrum

🇳🇱

Veldhoven, Netherlands

Elkerliek Ziekenhuis

🇳🇱

Helmond, Netherlands

Netherlands Cancer Institute

🇳🇱

Amsterdam, Netherlands

Isala Klinieken Stichting

🇳🇱

Zwolle, Netherlands

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

🇳🇱

Rotterdam, Netherlands

Catharina Ziekenhuis Stichting

🇳🇱

Eindhoven, Netherlands

Stichting St. Anna Zorggroep

🇳🇱

Geldrop, Netherlands

Maastricht University Medical Center

🇳🇱

Maastricht, Netherlands

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Amsterdam UMC
🇳🇱Amsterdam, Netherlands
Jurriaan Tuynman
Site contact
+31204441100
j.tuynman@amsterdamumc.nl

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