Acronym

PelvEx II

Name of the study

Multicenter, open-label, randomised, controlled, parallel arms clinical trial of induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer

Researchers and contact information

Project Leader

Dr. J.W.A. (Pim) Burger
E: pim.burger@catharinaziekenhuis.nl

 

Coordinating investigators 

Drs. S. (Stefi) Nordkamp

Drs. F. (Floor) Piqeur
E: pelvex2@catharinaziekenhuis.nl
T: +31 (0)40 2398858

Summary study

Rationale
Patients with locally recurrent rectal cancer (LRRC) have a poor prognosis. The most important prognostic factor for survival after surgery is a clear resection margin (R0 resection). Currently, a R0 resection is achieved in approximately 60% of patients. Adding induction chemotherapy to the neoadjuvant treatment regimen of patients with LRRC may increase downsizing of the tumour and thereby result in more R0 resections. Increasing the R0 resection rate may subsequently decrease local re-recurrence and thereby improve quality of life and survival in patients with LRRC. In addition, induction chemotherapy may have the potential to eradicate micrometastases.  

Study design
International, multicentre, open-label, phase III, parallel arms randomised controlled trial.
Inclusion of patients and surgery are limited to expert centres, defined as centres that perform at least 10 resections of LRRC per year. Induction chemotherapy and chemoradiotherapy may be administered in expert centres and selected non-expert centres.

Study population
Patients ≥18 years with a good performance status (WHO 0-1) who are diagnosed with resectable locally recurrent rectal cancer after total or partial mesorectal resection, without radiological evidence of systemic metastasis disease or radiotherapy and/or chemotherapy in the past 6 months and no contraindication for the planned chemotherapy, chemoradiotherapy and/or surgery or concurrent malignancies that interfere with the planned study treatment or prognosis of resected LRRC.

Primary endpoint
The proportion of patients with a clear resection margin (R0 resection).

Secondary endpoint
Local re-recurrence free survival, progression free survival, metastasis free survival, disease free survival, overall survival, radiological response, pathologic response, treatment related toxicity and compliance, number of patients undergoing surgery, surgical characteristics, major post-operative morbidity, quality of life and costs.

Sample size
The expected R0 resection rate is 60% in the experimental arm and 45% in the control arm (taking into account that 25% of patients starting with neoadjuvant treatment are not eligible for surgery due to progressive disease). A total of 364 patients (173 per arm) is required to detect this difference with α of 0.05, β of 0.80 and a drop-out of 5%.

Intervention

Control arm
Chemoradiotherapy followed by surgery

Experimental arm
Induction chemotherapy followed by chemoradiotherapy and surgery

 

 

 

Participating expert centers

• Catharina Ziekenhuis
• Antoni van Leeuwenhoek Ziekenhuis
• Erasmus Medisch Centrum
• Universitair Medische Centrum Groningen
• Maastricht Universitair Medisch Centrum
• Haaglanden Medisch Centrum
• Leids Universitair Medisch Centrum
• Amsterdam Universitair Medisch Centrum - Locatie VUmc en AMC
• Karolinska Instutet - Stockholm
• Skane University Hospital - Malmo
• Sahlgrenska University Hospital - Gothenburg

 

Participating centres (neoadjuvant treatment only)

• Isala
• Medisch Spectrum Twente
• Admiraal de Ruyter Ziekenhuis
• Radiotherapiegroep
• Zuidwest Radiotherapeutisch Instituut
• Amphia Ziekenhuis
• Jeroen Bosch Ziekenhuis
• Rijnstate
• Instituut Verbeeten
• St. Antonius Ziekenhuis
• Radboud Universitair Medisch Centrum
• Medisch Centrum Leeuwarden
• Universitair Medisch Centrum Utrecht
• Elisabeth TweeSteden Ziekenhuis
• Maastro Clinic

 

Planned participating centres

• Radiotherapeutisch Instituut Friesland
• Universitair ziekenhuis Gent
• Instituto Portugues de Oncologia de Lisboa Francisco Gentil - Lissabon
• Bravis Ziekenhuis
• Gelre Ziekenhuizen