Acronym

OPAXX

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

Principal investigators:

Brechtje Grotenhuis, MD, PhD, dept. Surgery, Antoni van Leeuwenhoek.

E: b.a.grotenhuis@nki.nl

Pim Burger, MD, PhD, dept. Surgery, Catharina Hospital Eindhoven

E: pimburger@catharinaziekenhuis.nl

Study coordinator:

Barbara Geubels, MD, dept. Surgery, Antoni van Leeuwenhoek & Catharina Hospital Eindhoven

Plesmanlaan 121, 1066 CX Amsterdam, Postbox 90203

E: b.geubels@nki.nl / waitandseerectum@nki.nl
Phone: 020-5129001

Website: www.opaxx.nl

Summary study

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.

 Inclusion criteria:

• 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);

Exclusion criteria:

• 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;

Intervention

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.

OPAXX flow-chart:

 

 

 

 

 

 

Participating centers:

1. Antoni van Leeuwenhoek
2. Catharina Hospital Eindhoven
3. Isala Zwolle
4. Medical Center Leeuwarden
5. 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