Trial Title:
Organ Preservation in Rectal Cancer: Contact X-ray Brachytherapy vs Extending the Waiting Interval and Local Excision
NCT ID:
NCT05772923
Condition:
Organ Preservation
Rectal Cancer
Quality of Life
Locally Advanced Rectal Carcinoma
Conditions: Official terms:
Rectal Neoplasms
Conditions: Keywords:
Organ preservation
Rectal cancer
(Chemo)radiation
Local excision
Contact x-ray brachytherapy
TAMIS
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
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).
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
Contact x-ray brachytherapy
Description:
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.
Arm group label:
Contact x-ray brachytherapy
Intervention type:
Procedure
Intervention name:
Local excision
Description:
Local excision will basically be performed by the TAMIS-procedure (transanal minimally
invasive surgery).
Arm group label:
Extending the waiting interval, with or without local excision
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.
Detailed description:
Rationale: The organ preservation approach for rectal cancer has been explored
increasingly, aiming at improving quality of life by prevention of total mesorectal
excision (TME-surgery). In patients with intermediate rectal cancer (IRC) and locally
advanced rectal cancer (LARC) who receive neoadjuvant (chemo)radiotherapy (in general a
short-course radiotherapy or a long-course chemoradiation, respectively) subsequent
TME-surgery is still standard of care.
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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.
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;
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Medical Center Leeuwarden
Address:
City:
Leeuwarden
Zip:
8934 AD
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Hoff, MD
Phone:
058 286 6666
Email:
c.hoff@mcl.nl
Facility:
Name:
Radbouw University Medical Centre
Address:
City:
Nijmegen
Zip:
6500 HB
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
de Wilt, MD, PhD
Phone:
024 361 1111
Email:
hans.dewilt@radboudumc.nl
Facility:
Name:
Catharina Hospital
Address:
City:
Eindhoven
Zip:
5623EJ
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Burger, MD, PhD
Phone:
040 239 9111
Email:
pim.burger@catharinaziekenhuis.nl
Facility:
Name:
Antoni van Leeuwenhoek
Address:
City:
Amsterdam
Zip:
1066CX
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Grotenhuis, MD, PhD
Phone:
020-5129111
Email:
b.grotenhuis@nki.nl
Facility:
Name:
Deventer Hospital
Address:
City:
Deventer
Zip:
7416 SE
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Talsma, MD, PhD
Phone:
0570 535 353
Email:
k.talsma@dz.nl
Facility:
Name:
Isala
Address:
City:
Zwolle
Zip:
8025 AB
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
van Westreenen, MD, PhD
Phone:
088 624 5000
Email:
h.l.van.westreenen@isala.nl
Facility:
Name:
Ijsselland Hospital
Address:
City:
Capelle Aan Den IJssel
Zip:
2906 ZC
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Vermaas, MD, PhD
Phone:
010 258 5000
Email:
mvermaas@ysl.nl
Start date:
April 16, 2021
Completion date:
March 2029
Lead sponsor:
Agency:
The Netherlands Cancer Institute
Agency class:
Other
Collaborator:
Agency:
Catharina Ziekenhuis Eindhoven
Agency class:
Other
Collaborator:
Agency:
ZonMw: The Netherlands Organisation for Health Research and Development
Agency class:
Other
Source:
The Netherlands Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05772923
https://www.opaxx.nl/
