Organ Preservation in Rectal Cancer: Contact X-ray Brachytherapy vs Extending the Waiting Interval and Local Excision

NCT05772923 | Recruiting DMC

• 1 other identifier: M20PAX
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 7

Brief Summary

The goal of this prospective phase II feasibility study is to evaluate two additional local treatment options in rectal cancer patients with a good clinical response after neoadjuvant (chemo)radiation: contact x-ray brachytherapy versus extension of the waiting interval with or without local excision, and to investigate which rate of organ preservation can be achieved.

Conditions

Organ Preservation; Rectal Cancer; Quality of Life; Locally Advanced Rectal Carcinoma

Keywords

Organ preservation; Rectal cancer; (Chemo)radiation; Local excision; Contact x-ray brachytherapy; TAMIS

Outcome Measures

Primary Outcomes (1)

• Rate of successful organ preservation

  Including an in-situ rectum (including patients subjected to local excision), no defunctioning stoma and absence of active loco-regional cancer failure (indicated as either local intraluminal tumour regrowth or regional recurrence in lymph nodes requiring TME-surgery)

  At one year following randomisation

Secondary Outcomes (11)

• Incidence of radiation toxicity

  Short-term (< 3 months after end of treatment) and long-term (< 12 months after end of treatment)

• Incidence of postoperative morbidity after local excision

  Short term (occurring within 3 months after local excision) and long-term (within one year)

• Frequency of patients with a high Low Anterior Rectal Syndrome (LARS) score

  At baseline, at 3 months, one, two and five year

• Frequency of patients with impaired of bowel function

  At baseline, at 3 months, one, two and five year

• Frequency of patients with impaired bladder function

  At baseline, at 3 months, one, two and five year

Study Arms (2)

Contact x-ray brachytherapy

EXPERIMENTAL

Contact x-ray brachytherapy will be given 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.

Radiation: Contact x-ray brachytherapy

Extending the waiting interval, with or without local excision

EXPERIMENTAL

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.

Procedure: Local excision

Interventions

Contact x-ray brachytherapy RADIATION

With contact x-ray brachytherapy an intraluminal radiation boost up to 90 Gy is applied to the primary rectal tumour, with minimal collateral damage to the surrounding normal tissues due to minimal penetration of the 50 kVolt therapy.

Contact x-ray brachytherapy

Local excision PROCEDURE

Local excision will basically be performed by the TAMIS-procedure (transanal minimally invasive surgery).

Extending the waiting interval, with or without local excision

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• histologically verified adenocarcinoma above the dentate line and within 10cm of the anal verge;
• neoadjuvant short-course radiotherapy for patients with 1) IRC and delayed response evaluation according to the Dutch national guidelines (cT1-3, cN1-2 lymph nodal status, no involved MRF or cT3c-d, N0-1 lymph nodal status without pres-ence of significant distant metastases) without full dose chemotherapy in the inter-val (e.g. Rapido-scheme) or 2) LARC due to comorbidity or frailty; OR
• neoadjuvant long-course radiotherapy (chemoradiation) for patients with 1) LARC 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 rectal cancer or IRC 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);
• age \>18 years;
• written informed consent.

You may not qualify if:

• 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;

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Catharina Ziekenhuis Eindhoven: collaborator
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (7)

Radbouw University Medical Centre

Nijmegen, Gelderland, 6500 HB, Netherlands

RECRUITING

Catharina Hospital

Eindhoven, North Brabant, 5623EJ, Netherlands

RECRUITING

Antoni van Leeuwenhoek

Amsterdam, North Holland, 1066CX, Netherlands

RECRUITING

Deventer Hospital

Deventer, Overijssel, 7416 SE, Netherlands

RECRUITING

Isala

Zwolle, Overijssel, 8025 AB, Netherlands

RECRUITING

Medical Center Leeuwarden

Leeuwarden, Provincie Friesland, 8934 AD, Netherlands

RECRUITING

Ijsselland Hospital

Capelle aan den IJssel, South Holland, 2906 ZC, Netherlands

RECRUITING

Related Publications (1)

• Geubels BM, van Triest B, Peters FP, Maas M, Beets GL, Marijnen CAM, Custers PA, Rutten HJT, Theuws JCM, Verrijssen AE, Cnossen JS, Burger JWA, Grotenhuis BA. Optimisation of Organ Preservation treatment strategies in patients with rectal cancer with a good clinical response after neoadjuvant (chemo)radiotherapy: Additional contact X-ray brachytherapy versus eXtending the observation period and local excision (OPAXX) - protocol for two multicentre, parallel, single-arm, phase II studies. BMJ Open. 2023 Dec 30;13(12):e076866. doi: 10.1136/bmjopen-2023-076866.

  PMID: 38159950 DERIVED

Related Links

• study website

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Mastectomy, Segmental

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Mastectomy; Surgical Procedures, Operative

Study Officials

• Brechtje A Grotenhuis, MD, PhD

  Antoni van Leeuwenhoek Hospital

  PRINCIPAL INVESTIGATOR

• Pim Burger, MD, PhD

  Catharina Ziekenhuis Eindhoven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Barbara M Geubels, MD

CONTACT

0205129001; b.geubels@nki.nl

Brechtje A Grotenhuis, MD, PhD

CONTACT

020 239 9111; b.grotenhuis@nki.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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): two parallel single study-arms evaluate the efficacy of experimental organ preservation approaches. To allow for a better comparison of secondary parameters (toxicity and morbidity of both additional local treatments) eligible patients will be randomized between two experimental arms. Furthermore, an observational cohort study is established to register rectal cancer patients with a good but not complete clinical response after (chemo)radiation who are not eligible for randomisation in the OPAXX study (OPAXX registration study).

Study Record Dates

• First Submitted: March 4, 2021
• First Posted: March 17, 2023
• Study Start: April 16, 2021
• Primary Completion: March 1, 2025
• Study Completion (Estimated): March 1, 2029
• Last Updated: March 17, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (7)