Clinical trial NCT06087718: Feasibility of the Maastro Applicator in Rectal Cancer
Official title: Introduction of the Maastro Applicator for Endoluminal Boosting in Rectal Cancer: a Pilot Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Rectal Cancer
Feasibility
Toxicity
Quality of Life
Radiation Toxicity
Radiation Proctitis
Brachytherapy
Complete Response
Lead sponsor: Maastricht Radiation Oncology
Sponsor class: OTHER
Collaborators: name: Varian Medical Systems
First posted: 2023-10-18
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: A single arm prospective interventional pilot trial in 10 patients with feasibility and safety checks and early stopping/intermission rules
Primary purpose: TREATMENT

Brief summary: The goal of this interventional pilot trial is to confirm that Maastro endoluminal HDR ( High Dose Radiation) contact brachytherapy boosting is feasible and may increase the chance of functional organ sparing of the rectum in patients with rectal cancer. Participants will be treated with chemoradiotherapy and an endoluminal boost with the Maastro applicator.

Detailed description: The goal of this clinical trial is to confirm that Maastro endoluminal HDR contact brachytherapy boosting is feasible and may increase the chance of functional organ sparing of the rectum in patients with rectal cancer. If at least 7 out of 10 planned Maastro applicator treatment series (3 fractions per series) can be conducted successfully from a procedural point of view the treatment will be considered feasible. The study intervention will be similar to the study treatment of arm B of the OPERA trial. Opposed to the treatment in arm B of the OPERA trial, the endoluminal boost will be given using HDR brachytherapy with the Maastro applicator instead of a CXRT (Contact X-ray Radiotherapy) device. The dose profile of the Maastro applicator is similar to the dose profile of CXRT device. As in the OPERA trial patients will be stratified based on tumor size. As the diameter of the treatment field of the largest Maastro applicator (there are two sizes) equals 2.5 cm we will stratify for tumor diameter \< 2.5 cm v ≥ 2.5 cm. In the OPERA trial patients were stratified for a tumor diameter of \< 3.0 cm v ≥ 3.0 cm as currently the largest applicator diameter for the CXRT device is 3.0 cm (currently available applicators: 2.0, 2.5 and 3.0 cm). The endoluminal boost will consist of 3 fractions with a dose equivalent to 30 Gy per fraction prescribed at the surface of the applicator. The 3 boost fractions will be delivered over a 4-week time period (week 1-2-4). Conform OPERA protocol, patients with a tumor size \< 2.5 cm will receive an upfront endoluminal HDR contact boost followed by concurrent chemoradiotherapy (25x1.8 Gy combined with capecitabine 825 mg/m2 bd on radiotherapy days). Patients with a tumor size ≥ 2.5 cm will first undergo concurrent chemoradiotherapy (25x1.8 Gy combined with capecitabine 825 mg/m2 bd on radiotherapy days) to first shrink the tumor and will receive the endoluminal HDR contact boost afterwards in order to eventually fit the tumor surface in the surface of the Maastro applicator.

Eligibility criteria: Inclusion Criteria:

* ≥ 18 years of age and capable of giving informed consent.
* Adenocarcinoma of the rectum classified cT (clinical Tumor) 2-3b, \< 5 cm largest diameter and \< ½ circumference (MRI staging), N0-N1 (any node \< 8 mm diameter), M0
* Operable patient
* Tumor accessible to the Maastro applicator with a distance from the lower tumor border to the anal verge ≤10 cm
* No comorbidity preventing treatment
* Adequate birth control for women of child-bearing potential
* Follow-up possible.

Exclusion Criteria:

* Tumor extending into the anal canal.
* Stop of anti-coagulants (except ≤100 mg aspirin/day) is medically contraindicated.
* Presence of coagulation disorder resulting in an increased bleeding risk.
* Prior pelvic radiation therapy (excluding the abovementioned neoadjuvant treatment).
* Prior surgery or chemotherapy for rectal cancer (excluding the abovementioned neoadjuvant treatment).
* Inflammatory bowel disease (IBD).
* (Systemic) treatment possibly causing rectal or genitourinary toxicity for a separate active malignancy.
* World Health Organization performance status (WHO-PS) ≥ 3.
* Life expectancy of \< 6 months.
* Pregnant women.

Primary outcomes:
measure: Clinical feasibility of the Maastro boosting technique.
timeFrame: During treatment
Secondary outcomes:
measure: Efficacy of Maastro applicator endoluminal HDR contact brachytherapy boosting in functional organ sparing of the rectum
timeFrame: 3 years follow-up
measure: Percentage of planned interventional Maastro procedures that could be conducted successfully from a procedural point of view.
timeFrame: During treatment
measure: Duration of the application procedure.
timeFrame: During treatment
measure: Percentage of patients with G3 or higher rectal toxicity up to 3 months after treatment potentially attributable to endoluminal HDR contact brachytherapy.
timeFrame: 3 months follow-up
measure: Clinical complete response rate up to 3 years after treatment.
timeFrame: 3 years follow-up
measure: Rectal toxicity scored according to CTCAE v. 5 up to 3 years after treatment.
timeFrame: 3 years follow-up
measure: Genitourinary toxicity scored according CTCAE v. 5 up to 3 years after treatment.
timeFrame: 3 years follow-up
measure: Health status and quality of life as measured by QLQ (quality of life questionnaire)-C30 up to 3 years after treatment.
timeFrame: 3 years follow-up
measure: Health status and quality of life as measured by QLQ-CR29 (Colo Rectal) up to 3 years after treatment.
timeFrame: 3 years follow-up
measure: Health status and quality of life as measured by EQ-5D (EuroQol Five Dimensions Health Questionnaire) up to 3 years after treatment.
timeFrame: 3 years follow-up
measure: Long-term rectal functional outcome as measured by LARS 9 Low Anterior Resection Syndrome) score up to 3 years after treatment.
timeFrame: 3 years follow-up
measure: Local recurrence rate up to 5 years after treatment.
timeFrame: 5 years follow-up
measure: Locoregional recurrence rate up to 5 years after treatment.
timeFrame: 5 years follow-up
measure: Metastatic rate up to 5 years after treatment.
timeFrame: 5 years follow-up
measure: Salvage surgery rate after treatment.
timeFrame: 5 years follow-up
measure: Overall and disease specific survival rate up to 5 year after treatment.
timeFrame: 5 years follow-up
measure: The diagnostic value of clinical response assessment using digital rectal examination, endoscopy and MRI after endoluminal radiation boosting using the Maastro applicator.
timeFrame: during follow-up
measure: Complications within the first 30 days after completion of salvage total mesorectal excision (TME) surgery up to 3 years after treatment.
timeFrame: 3 years follow-up
Other outcomes:
measure: Collecting 3D ultrasound measurements of the gross tumor volume (GTV) and intestinal wall layers at every fraction of Maastro applicator brachytherapy.
timeFrame: During treatment
Locations:
Study officials:
affiliation: Maastro, the Netherlands
name: Maaike Berbée, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bellezzo M, Fonseca GP, Verrijssen AS, Voncken R, Van den Bosch MR, Yoriyaz H, Reniers B, Berbee M, Van Limbergen EJ, Verhaegen F. A novel rectal applicator for contact radiotherapy with HDR 192Ir sources. Brachytherapy. 2018 Nov-Dec;17(6):1037-1044. doi: 10.1016/j.brachy.2018.07.012. Epub 2018 Aug 16.
citation: Bellezzo M, Fonseca GP, Voncken R, Verrijssen AS, Van Beveren C, Roelofs E, Yoriyaz H, Reniers B, Van Limbergen EJ, Berbee M, Verhaegen F. Advanced design, simulation, and dosimetry of a novel rectal applicator for contact brachytherapy with a conventional HDR 192Ir source. Brachytherapy. 2020 Jul-Aug;19(4):544-553. doi: 10.1016/j.brachy.2020.03.009. Epub 2020 May 6.
citation: Gerard JP, Barbet N, Schiappa R, Magne N, Martel I, Mineur L, Deberne M, Zilli T, Dhadda A, Myint AS; ICONE group. Neoadjuvant chemoradiotherapy with radiation dose escalation with contact x-ray brachytherapy boost or external beam radiotherapy boost for organ preservation in early cT2-cT3 rectal adenocarcinoma (OPERA): a phase 3, randomised controlled trial. Lancet Gastroenterol Hepatol. 2023 Apr;8(4):356-367. doi: 10.1016/S2468-1253(22)00392-2. Epub 2023 Feb 16.