Induction Chemotherapy for Locally Recurrent Rectal Cancer

Phase 3RecruitingNCT04389086

Catharina Ziekenhuis Eindhoven364 enrolled

Overview

This is a multicentre, open-label, parallel arms, phase IIII study that randomises patients with locally recurrent rectal cancer in a 1:1 ratio to receive either induction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

364

Conditions

Recurrent Rectal Cancer

Interventions

Combination drugDRUG

Induction chemotherapy consists of either three three-weekly cycles of CAPOX (oxaliplatin 130 mg/m2 BSA IV + capecitabine 1000 mg/m2 BSA, orally, twice daily) or four two-weekly cycles of FOLFOX (85 mg/m2 BSA of oxaliplatin IV + 400 mg/m2 BSA of leucovorin IV + 400 mg/m2 BSA of bolus 5-fluorouracil IV followed by 2400 mg/m2 BSA of continuous 5-fluorouracil IV). It is left to the discretion of the treating medical oncologist which of the two will be administered. In case of (previous) unacceptable toxicity (physician's discretion) to oxaliplatin, FOLFIRI may be prescribed. FOLFIRI (180 mg/m2 BSA of irinotecan IV + 400 mg/m2 BSA of leucovorin IV + 400 mg/m2 BSA of bolus 5-fluorouracil IV followed by 2400 mg/m2 BSA of continuous 5-fluorouracil IV) consists of four two-weekly cycles. If a patient has stable or responsive disease, induction chemotherapy will be continued with either one three-weekly cycle of CAPOX or two two-weekly cycles of FOLFOX/FOLFIRI.

ChemoradiotherapyRADIATION

Concomitant chemotherapy agent: capecitabine Radiotherapy dose: full course radiotherapy consists of 25x2.0 or 28x1.8 Gy. In case of previous radiotherapy, the radiotherapy dose will consist of 15x2.0 Gy.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 18 years or older * Confirmed locally recurrent rectal cancer after total or partial mesorectal resection for rectal or distal sigmoidal cancer either by histopathology ór clinically proven (evidence on imaging in combination with clinical findings, with consensus in MDT) * Resectable disease determined by magnetic resonance imaging (MRI) or deemed resectable after neoadjuvant treatment with chemoradiotherapy. * WHO performance score 0-1 * Written informed consent Exclusion Criteria: * Radiological evidence of metastatic disease (e.g. liver, lung) at time of randomisation or in the six months prior to randomisation. * Known homozygous DPD deficiency * Any chemotherapy in the past 6 months. * Any contraindication for the planned chemotherapy, as determined by the medical oncologist. * Radiotherapy in the past 6 months for primary rectal cancer. * Any contraindication for the planned chemoradiotherapy, as determined by the medical oncologist and/or radiation oncologist. * Any contraindication for surgery, as determined by the surgeon and/or anaesthesiologist. * Concurrent malignancies that interfere with the planned study treatment or the prognosis of resected LRRC.

Locations (14)

UZ Gent

Ghent, Belgium

NOT_YET_RECRUITING

Amsterdam UMC

Amsterdam, Netherlands

RECRUITING

Outcomes

Primary Outcomes

Proportion of patients with a clear resection margin

A resection margin is considered clear (R0), if there are no tumour cells in any of the resection surfaces as determined by microscopy (resection margin \> 0mm)

Time frame: Scored within 1 one month of surgery