Clinical trial NCT06729645: External Beam Radiotherapy Combined with Endorectal High-dose-rate Brachytherapy in Elderly and Frail Patients with Rectal Cancer
Official title: ACO/ARO/AIO-22 - External Beam Radiotherapy Combined with Endorectal High-dose-ratebrachytherapy in Elderly and Frail Patients with Rectal Cancer. a Prospective Multicentre Trial of the German Rectal Cancer Study Group
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Rectal Cancer
Lead sponsor: University Hospital of Cologne
Sponsor class: OTHER
First posted: 2024-12-11
Enrollment: 80
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: ACO/ARO/AIO-22 - External beam radiotherapy combined with endorectal high-dose-ratebrachytherapy in elderly and frail patients with rectal cancer.

A prospective multicentre trial of the German Rectal Cancer Study Group.

Detailed description: Epidemiological data indicate that more than 50% of patients with newly-diagnosed rectal cancer are older than 70 years, with rising numbers expected over the next decades. Albeit total mesorectal excision (TME) is considered part of the standard multimodal therapy in rectal cancer, elderly and frail rectal cancer patients are often unable to undergo radical surgery as the risk of surgical complications and postoperative mortality rises with increasing age and comorbidity. In an analysis of the Colorectal Cooperative Group UK (1988-200) in 34.194 patients with colorectal cancer, 21% of those aged over 85 years did not undergo operation, while the rates of no surgical intervention were 11% in the 75-84 years age group. Furthermore, these patients often receive no treatment at all due to frailty and concurrent diseases, resulting in local and/or systemic disease progression with associated symptoms and impaired quality of life (QoL).

Significant advances have been made in modern radiotherapy (RT), which can provide a valuable alternative non-operative treatment strategy for elderly and frail patients. Notably, to achieve clinical complete response (cCR) with RT alone, high doses are needed. Recent data from randomized trials (OPERA, MORPEUS) in young and fit patients with rectal cancer indicate that increased RT doses can be safely delivered following external beam (chemo)radiotherapy (EBRT) followed by endoluminal radiotherapeutic modalities, such as contact X-ray brachytherapy (CXB) or high-dose rate endorectal brachytherapy (HDR-BT). However, prospective studies testing this therapeutic concept in elderly and frail patients with rectal cancer remain limited. Also, despite the wide availability of brachytherapy, applicability of this concept remains largely unexplored in this challenging age subgroup in Germany.

The ACO/ARO/AIO-22 prospective trial will aim to evaluate the efficacy of EBRT in combination with endorectal HDR-BT to achieve local control (cCR) and maintain QoL in elderly and frail patients with rectal cancer that are considered unfit for radical surgery, but amenable to EBRT in combination with endorectal HDR-BT or CXB.

The ACO/ARO/AIO-22 incorporates several aspects that make this prospective study important:

1. treatment decision making is challenging in elderly/frail patients with rectal cancer, whereas standardized treatment guidelines for this patient cohort are lacking, thus necessitating new clinical trials to establish the best possible treatment in this clinical setting;
2. the combination of EBRT and HDR-BT has been shown to result in high rates of tumor response with almost 90% overall response and cCR rates of approximately 50-80%, especially in young and fit patients with early stage tumors, whereas prospective trials in elderly/frail patients remain limited;
3. due to its very steep dose gradient, endorectal HDR-BT enables the delivery of a very high radiation dose to the tumor with a very steep decrease in the volume of normal tissue, thus increasing treatment efficacy while keeping toxicity low;
4. albeit already tested in different countries such as France, the Netherlands and the UK, the concept of combining EBRT with endorectal HDR-BT has not been widely tested in Germany yet and, thus, a prospective study is needed to evaluate its efficacy and safety in elderly/frail patients with rectal cancer, to develop expertise and to make this modality widely available for this challenging patient cohort.

Altogether, the concept of combining EBRT with endorectal HDR-BT to be tested as part of the ACO/ARO/AIO-22 prospective trial constitutes an attractive option in elderly/frail patients with rectal cancer unfit for radical surgery as it can potentially provide long-term local control of the primary tumor, prevent disease-related morbidity, prolong survival, improve QoL and even lead to cCR with complete cure in selected cases.

Eligibility criteria: Inclusion Criteria:

* Elderly patients (age ≥70 years) with a G8-frailty score ≤ 14 based on the G8 geriatric assessment tool of frailty and/or elderly patients (age ≥70 years) with American Society of Anesthesiologists Physical Status (ASA PS) ≥ 3 and/ elderly patients (age ≥70 years) unsuitable to tolerate radical surgery as judged by the surgeon and/or elderly patients (age ≥70 years) that refuse radical surgery
* Life expectancy ≥ 6 months
* Male and female patients with histologically confirmed diagnosis of rectal adenocarcinoma localized 0-16 cm from the anocutaneous line as measured by rigid rectoscopy
* MRI-defined cT1-3d N0/+ M0, mrCRM - / +, \</= 2/3 involvement of the rectal wall circumference
* Staging requirements: High-resolution, thin-sliced (i.e. 3mm) magnetic resonance imaging (MRI) of the pelvis is the mandatory local staging procedure.
* Spiral-CT of the abdomen and chest to exclude distant metastases.

Exclusion Criteria:

* Previous or current drug abuse
* Other concomitant antineoplastic therapy
* Prior or concurrent malignancy ≤ 3 years prior to enrolment in study (Exception: non-melanoma skin cancer or cervical carcinoma FIGO stage 0-

  1), unless the patient is continuously disease-free
* Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule (these conditions should be discussed with the patient before registration in the trial).

Primary outcomes:
measure: Rate of Clinical Complete Response (cCR) or Near cCR at 12 Months
timeFrame: 12 Months
Secondary outcomes:
measure: Quality of Life and Functional Outcomes
timeFrame: 2 years
Other outcomes:
measure: Translational/Biomarker Studies
timeFrame: 6 months
Locations:
city: Kempten
country: Germany
facility: Klinikverbund Allgäu
state: BaBaden-Württembergs
city: Frankfurt
country: Germany
facility: Frankfurt Universitätsklinikum
state: Hessen
city: Cologne
country: Germany
facility: Klinik für Strahlentherapie, Cyberknife und Radioonkologie Universität zu Köln
state: NRW
city: Leipzig
country: Germany
facility: Leipzig, Universitätsklinikum
state: Sachsen
Study officials:
affiliation: University Hospital of Cologne
name: Emmanouil Fokas, MD DPhil
role: STUDY_CHAIR
References:
citation: Fleischmann M, Diefenhardt M, Nicolas AM, Rodel F, Ghadimi M, Hofheinz RD, Greten FR, Rodel C, Fokas E; German Rectal Cancer Study Group. ACO/ARO/AIO-21 - Capecitabine-based chemoradiotherapy in combination with the IL-1 receptor antagonist anakinra for rectal cancer Patients: A phase I trial of the German rectal cancer study group. Clin Transl Radiat Oncol. 2022 Apr 6;34:99-106. doi: 10.1016/j.ctro.2022.04.003. eCollection 2022 May.