Name of the study
OPAXX: Organ Preservation in patients with a good clinical response after neoadjuvant (chemo)radiation for rectal cancer: optimization of treatment strategies and defining the role of Adittional contact X-ray Brachytherapy versus eXtending the waiting interval and local excision
Researchers and contact information
Brechtje Grotenhuis, MD, PhD, dept. Surgery, Antoni van Leeuwenhoek.
Pim Burger, MD, PhD, dept. Surgery, Catharina Hospital Eindhoven
Barbara Geubels, MD, dept. Surgery, Antoni van Leeuwenhoek & Catharina Hospital Eindhoven
Plesmanlaan 121, 1066 CX Amsterdam, Postbox 90203
E: firstname.lastname@example.org / email@example.com
Objective: The aim of this study is to investigate which rate of organ preservation can be achieved in patients with rectal cancer treated with neoadjuvant (chemo)radiotherapy with a clinically good, but not complete response, and to optimize the different treatment strategies. In patients with a near-complete response or with a small residual tumour mass, participation is offered in a phase II feasibility trial, in which two potential organ preservation treatment strategies are evaluated: contact x-ray brachytherapy or extension of the waiting interval with or without additional local excision in case of residual disease.
Study population: Rectal cancer patients receiving neoadjuvant (chemo)radiotherapy are eligible for this study when at the first response assessment (6-8 weeks after finishing the (chemo)radiation) a good, but not complete clinical response is seen: a near-complete response or a small residual tumour mass <3 cm without evidence of residual nodal disease.
Study design: This is a prospective study with a mixed design. It concerns a phase II feasibility study for patients in whom a good, but not complete response has been achieved after (chemo)radiation (OPAXX study). Eligible patients will be randomized between two parallel study arms: contact x-ray brachytherapy versus extending the waiting interval +- local excision. For patients with a good but not complete clinical response after (chemo)radiation who are not eligible for randomisation in the OPAXX study an observational cohort study is conducted (OPAXX registration study).
Endpoints: The primary endpoint is the rate of successful organ preservation at one year (defined as an in-situ rectum, no defunctioning stoma and absence of active locoregional cancer failure). Secondary endpoints are functional and oncological outcomes, morbidity and toxicity of additional local treatment.
- histologically verified adenocarcinoma above the dentate line and within 10cm of the anal verge;
- neoadjuvant short-course radiotherapy for patients with 1) intermediate rectal cancer and delayed response evaluation according to the Dutch national guidelines (cT1-3, cN1-2 lymph nodal status, MRF- or cT3c-d, N0-1 lymph nodal status without presence of significant distant metastases) without full dose chemotherapy in the interval (e.g. Rapido-scheme) or 2) locally advanced rectal cancer due to comorbidity or frailty; OR
- neoadjuvant long-course radiotherapy (chemoradiation) for patients with 1) locally advanced rectal cancer according to the Dutch national guidelines (cT4 tumour, cN2 lymph nodal status, lateral lymph node involvement, and/or involved MRF, without the presence of significant distant metastases) or 2) early or intermediate rectal cancer and a strong wish for organ preservation;
- clinically near-complete response or a small residual tumour mass <3 cm;
- technically feasible to perform both treatment options (contact x-ray brachytherapy or local excision);
- neoadjuvant or induction chemotherapy prior or adjacent to (chemo)radiation, e.g. patients with a Rapido or M1-scheme are not eligible;
- radiation dose >50.4 Gy or boost dose on the primary tumour;
- presence of suspicious lymph nodes (yN1/N2) at first response evaluation;
- residual tumour ≥ 3cm or over half of the circumference of the rectal lumen;
- patients who are unable to undergo contact x-ray brachytherapy or local excision;
- patients who cannot tolerate a completion- or salvage-TME because of comorbidity or frailty;
Arm 1: Contact x-ray brachytherapy will be applied after randomisation with a maximum interval of 14 weeks after finishing the neoadjuvant (chemo)radiation. Contact x-ray brachytherapy consists of three fractions of 30Gy per fraction applied to the tumour, with a 2 week interval between each boost. Response evaluation takes place every 3 months thereafter. Patients in whom a clinical complete response is detected during follow-up are offered a watch-and-wait approach; patients in whom an incomplete response or disease progression is noted, completion or salvage TME-surgery is advised.
Arm 2: The waiting interval will be extended with 6-8 more weeks after the first response evaluation, followed by a second (or third in case of ongoing response) re-assessment. Patients with a clinical complete response at the time of the second (or third) response evaluation will be offered a watch-and-wait approach without any surgical treatment. Patients with a remaining small lesion will be offered transanal local excision. Depending on the final pathological staging after local excision, patients are categorized as low-risk or high-risk, and will be offered a watch-and-wait strategy or completion TME-surgery, respectively.
- Antoni van Leeuwenhoek
- Catharina Hospital Eindhoven
- Isala Zwolle
- Medical Center Leeuwarden
- IJsselland Hospital
Opening soon: Deventer Hospital, Radboud University Medical Center
Awaiting local approval: Maastricht University Medical Center, Amsterdam University Medical Center, Elisabeth-Tweesteden Ziekenhuis, Leiden University Medical Center