Induction Chemotherapy for Locally Recurrent Rectal Cancer
- Conditions
- Recurrent Rectal Cancer
- Interventions
- Drug: Combination drugRadiation: ChemoradiotherapyProcedure: Surgery locally recurrent rectal cancer
- Registration Number
- NCT04389086
- Lead Sponsor
- Catharina Ziekenhuis Eindhoven
- Brief Summary
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)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 364
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Induction chemotherapy + chemoradiotherapy + surgery Combination drug Induction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery Induction chemotherapy + chemoradiotherapy + surgery Surgery locally recurrent rectal cancer Induction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery Neoadjuvant chemotherapy + surgery Chemoradiotherapy Neoadjuvant chemoradiotherapy followed by surgery Induction chemotherapy + chemoradiotherapy + surgery Chemoradiotherapy Induction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery Neoadjuvant chemotherapy + surgery Surgery locally recurrent rectal cancer Neoadjuvant chemoradiotherapy followed by surgery
- Primary Outcome Measures
Name Time Method Proportion of patients with a clear resection margin Scored within 1 one month of surgery 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)
- Secondary Outcome Measures
Name Time Method Local recurrence free survival Assessed up to 5 years Progression free survival Assessed up to 5 years Metastasis free survival Assessed up to 5 years Overall survival Assessed up to 5 years Toxicity induction chemotherapy Scored until one month after the last administration of the chemotherapy Adverse events grade 3 or higher according to the NCI-CTCAE v5.0
Major surgical morbidity 30 and 90-days postoperative Clavien-Dindo grade 3 or higher
Radiological response Restaging is performed after 3 cycles of CAPOX (1 cycle is 3 weeks) or 4 cycles of CAPOX/FOLFOX (1 cycle is 2 weeks). Second restaging is performed 4-6 weeks after finishing chemoradiotherapy mrTRG
Cost-effectiveness at baseline, 3 months and 12 months postoperative EQ-5D-5L
Disease free survival Assessed up to 5 years Pathologic response Scored within 1 month of surgery Scored according to Mandard
Toxicity chemoradiotherapy Scored until 3 months after the last administration of the radiotherapy Adverse events grade 3 or higher according to the NCI-CTCAE v5.0
Compliance chemoradiotherapy Evaluation at time of surgery Surgical characteristics Evaluation directly postoperative including data on intra-operative radiotherapy
Colorectal cancer specific quality of life at baseline, 3 months and 12 months postoperative QLQ-CR29
Number of patients undergoing surgery Surgery is scheduled 10-14 weeks after finishing chemoradiotherapy Cancer specific quality of life at baseline, 3 months and 12 months postoperative QLQ-C30
Compliance induction chemotherapy Scored within 1 month after start chemoradiotherapy
Trial Locations
- Locations (14)
Haaglanden Medical Centre
🇳🇱Leidschendam, Netherlands
Oslo Universitetssykehus
🇳🇴Oslo, Norway
UZ Gent
🇧🇪Gent, Belgium
Antoni van Leeuwenhoek
🇳🇱Amsterdam, Netherlands
Catharina Hospital
🇳🇱Eindhoven, Netherlands
University Medical Centre Groningen
🇳🇱Groningen, Netherlands
Leids University Medical Centre
🇳🇱Leiden, Netherlands
Maastricht University Medical Centre
🇳🇱Maastricht, Netherlands
Erasmus Medical Centre
🇳🇱Rotterdam, Netherlands
Amsterdam UMC
🇳🇱Amsterdam, Netherlands
Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E.
🇵🇹Lisbon, Portugal
Sahlgrenska Universitetssjukhuset
🇸🇪Göteborg, Sweden
Skåne Universitetssjukhuset
🇸🇪Malmö, Sweden
Karolinska Universitetssjukhuset
🇸🇪Stockholm, Sweden