Organ Preservation in Rectal Cancer: Contact X-ray Brachytherapy vs Extending the Waiting Interval and Local Excision
NCT ID: NCT05772923
Last Updated: 2023-03-17
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
NA
168 participants
INTERVENTIONAL
2021-04-16
2029-03-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Organ Preservation in Locally Advanced Rectal Cancer by Radiochemotherapy Followed by Consolidation Chemotherapy.
NCT03561142
Longterm Functional Outcomes in Patients Undergoing Organ Preserving Treatment for Rectal Cancer With or Without Local Excision After Chemoradiotherapy
NCT06249672
Functional Outcome of Organ Preservation After Neo-adjuvant Chemo Radiation for Rectal Cancer
NCT02278653
Organ-preserving Management in Patients With Complete or Near-complete Tumour Response After Preoperative Radio(Chemo)Therapy for Rectal Cancer
NCT04095468
Implementation of a Tumor Response Assessment Program Integrating the Shared Medical Decision Into the Organ Preservation Strategy for Rectal Cancer Patients
NCT06740357
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
In patients with a good clinical response after neoadjuvant (chemo)radiation, organ preservation may be considered, depending on the extent of the response monitored by radiological and endoscopic assessment. Some patients show a clinical complete response and can be monitored closely in a watch-and-wait approach. In case of a good, but not complete response, it remains unclear which patients may benefit from extension of the observation period after (chemo)radiation in order to achieve a complete clinical response over time, or in whom additional local treatment options (such as contact x-ray brachytherapy or local excision) are beneficial in obtaining organ preservation eventually.
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 good clinical response, and to optimize the different treatment strategies. In patients with a near-complete response or 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 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): 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 population: In general, patients with IRC receiving short-course radiotherapy with delayed surgery (patients with initially a cT1-3, cN1-2 lymph nodal status, no involved MRF or cT3c-d, N0-1 lymph nodal status) or patients with LARC receiving neoadjuvant long-course chemoradiation (patients with initially cT4 tumour, cN2 lymph node status, lateral lymph node involvement and/or an involved mesorectal fascia (MRF+)) according to the Dutch national guideline are eligible for this study when at the first response assessment 6-8 weeks after finishing the (chemo)radiation a good clinical response is seen. A good clinical response has been defined as a clinical complete response, a near-complete response or a small residual tumour mass \<3 cm on endoscopy, but also no evidence of residual nodal disease on magnetic resonance imaging (MRI) (ycN0). In case of a clinical complete response the current strategy of watchful waiting is offered. Eligible patients in whom a good, but not complete response is detected will be randomized to one of the two experimental OPAXX study arms, provided that both additional local treatment options are technically feasible.
Intervention arms OPAXX study:
Arm 1: 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.
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.
Main study parameters/endpoints: The primary endpoint of the OPAXX study reflects the efficacy of both additional treatment options: the rate of successful organ preservation (defined as an in-situ rectum, no defunctioning stoma and absence of active locoregional cancer failure) at one year following randomisation in rectal cancer patients with a good, but not complete clinical response after (chemo)radiation. Secondary endpoints are related to toxicity and morbidity of the two additional treatment options in the randomisation study, as well as to oncological and functional outcomes at one, two and five years of follow-up.
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).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Standard treatment of IRC and LAR consists of neoadjuvant short-course or long-course (chemo)radiotherapy followed by TME-surgery. If a clinical complete response is seen at response evaluation, a watch-and-wait approach is currently considered a valid strategy in selected patients according to the Dutch national guidelines. In the ongoing Dutch national prospective registry patients with a near-complete response are currently offered an extension of the observation period rather than TME-surgery, and, subsequently, a watch-and-wait policy when a clinical complete response is noted over time. On the other hand, all patients with a persistent residual lesion will proceed to TME-surgery.
In the current study, two experimental approaches are introduced that could increase organ preservation rates in patients with a good, but not-complete response at the first response evaluation: additional endoluminal contact x-ray brachytherapy and local excision of the tumour remnant.
Prior to randomisation, eligible patients are well informed about the risks of the two experimental treatment strategies (i.e. unclear long-term oncological outcome), and are offered standard-of-care TME-surgery. Moreover, patients will be informed that additional treatment with contact x-ray brachytherapy or local excision might increase the morbidity rates in case completion or salvage TME-surgery is required.
Finally, in both arms of this phase II study an intensive surveillance program has been established, in order to detect treatment failure, tumour regrowth or disease recurrence at an early stage, in order to proceed to completion or salvage TME-surgery when needed and when possible.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Contact x-ray brachytherapy
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.
Contact x-ray brachytherapy
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.
Extending the waiting interval, with or without local excision
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.
Local excision
Local excision will basically be performed by the TAMIS-procedure (transanal minimally invasive surgery).
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Contact x-ray brachytherapy
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.
Local excision
Local excision will basically be performed by the TAMIS-procedure (transanal minimally invasive surgery).
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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.
Exclusion Criteria
* 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;
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Catharina Ziekenhuis Eindhoven
OTHER
ZonMw: The Netherlands Organisation for Health Research and Development
OTHER
The Netherlands Cancer Institute
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Brechtje A Grotenhuis, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Antoni van Leeuwenhoek Hospital
Pim Burger, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Catharina Ziekenhuis Eindhoven
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Radbouw University Medical Centre
Nijmegen, Gelderland, Netherlands
Catharina Hospital
Eindhoven, North Brabant, Netherlands
Antoni van Leeuwenhoek
Amsterdam, North Holland, Netherlands
Deventer Hospital
Deventer, Overijssel, Netherlands
Isala
Zwolle, Overijssel, Netherlands
Medical Center Leeuwarden
Leeuwarden, Provincie Friesland, Netherlands
Ijsselland Hospital
Capelle aan den IJssel, South Holland, Netherlands
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
References
Explore related publications, articles, or registry entries linked to this study.
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.
Related Links
Access external resources that provide additional context or updates about the study.
study website
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
M20PAX
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.