Clinical trial NCT05241574: Planned Non-operative Management for Rectal Cancer
Official title: Radio(Chemo)Therapy Dose Escalation in Non-operative Management for Rectal Cancer: A Prospective NOM-3 Observational Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: Rectal cancer
Non-operative management
Lead sponsor: Maria Sklodowska-Curie National Research Institute of Oncology
Sponsor class: OTHER
First posted: 2022-02-15
Enrollment: 23
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: A dose escalation study, either radiotherapy dose escalation or chemotherapy dose escalation.
Primary purpose: TREATMENT

Brief summary: The investigators propose to conduct an observational study on consecutive patients with low-lying or mid rectal cancers smaller than 5 cm in length and less than 50% of rectal circumferential extent. The aim of this study is to test a hypothesis that escalation of either radiation or chemotherapy dose of the routine preoperative radio(chemo)therapy leads to an increase of clinical complete response rate. The planned sample size of 23 patients was calculated based on the assumption that clinical complete response rate after routine preoperative radio(chemo)therapy is 34% \[1\] and expected rate after radio(chemo)therapy dose escalation is 75% \[2-4\]. An endorectal high dose rate iridium brachytherapy boost (2 fractions of 10 Gy) will be added after the routine preoperative treatment consisted of external beam radiotherapy (5 × 5 Gy) combined with sequential 3 cycles of consolidation FOLFOX4. However, for patients with involvement of the anal canal, additional 3 cycles of consolidation FOLFOX4 (6 cycles in total) will be added instead of brachytherapy boost to avoid severe post-radiation toxicity.


Eligibility criteria: Inclusion Criteria:

1. Adenocarcinoma of the rectum classified clinically as T2, T3a-c or T4b but only with superficial infiltration of the vagina or prostate; tumour accessible by digital rectal examination; tumour ≤5 cm in length and ≤50% of rectal circumferential extent; N0-N2, but mesorectal node \<7 mm and no lateral nodes enlargement); extramural vascular invasion but not larger than 7 mm in the largest dimension; M0.
2. Operable patient
3. Patient having read the information note and having signed the informed consent
4. Follow-up possible

Exclusion Criteria:

1. Inoperable patient
2. cT1, cT3d, large T4, tumour ≥5cm or ≥50 of rectal circumferential extent
3. Enlargement of lateral nodes or any node ≥8 mm in diameter
4. Patient presenting metastasis at diagnosis
5. Previous pelvic irradiation
6. Simultaneous progressive another cancer
7. Close follow-up uncertain.

Primary outcomes:
measure: Rate of patients with clinical complete response.
timeFrame: 15 weeks from the radiation start
Secondary outcomes:
measure: Regrowth rate.
timeFrame: From 12 months to 26 months from the radiation start.
measure: Anorectal function.
timeFrame: One year after the radiation start.
measure: Acute and late toxicity assessed by Common Terminology Criteria for Adverse Events (CTCAE), version 5.
timeFrame: From 12 months to 26 months from the radiation start.
Other outcomes:
Locations:
city: Warsaw
country: Poland
facility: M. Skłodowska-Curie National Research Institute of Oncology
Study officials:
affiliation: Maria Skłodowska-Curie National Research Institute of Oncology
name: Paulina Śliwka, MS
role: STUDY_DIRECTOR
References:
citation: Jankowski M, Pietrzak L, Rupinski M, Michalski W, Holdakowska A, Paciorek K, Rutkowski A, Olesinski T, Cencelewicz A, Szczepkowski M, Zegarski W, Reszke J, Richter P, Wawok P, Malecki K, Bebenek M, Szelachowska J, Mazurek M, Gisterek I, Polkowski W, Jankiewicz M, Stylinski R, Socha J, Bujko K; Polish Colorectal Study Group. Watch-and-wait strategy in rectal cancer: Is there a tumour size limit? Results from two pooled prospective studies. Radiother Oncol. 2021 Jul;160:229-235. doi: 10.1016/j.radonc.2021.05.014. Epub 2021 May 21.
citation: Garant A, Magnan S, Devic S, Martin AG, Boutros M, Vasilevsky CA, Ferland S, Bujold A, DesGroseilliers S, Sebajang H, Richard C, Vuong T. Image Guided Adaptive Endorectal Brachytherapy in the Nonoperative Management of Patients With Rectal Cancer. Int J Radiat Oncol Biol Phys. 2019 Dec 1;105(5):1005-1011. doi: 10.1016/j.ijrobp.2019.08.042. Epub 2019 Aug 30.
citation: Rijkmans EC, Cats A, Nout RA, van den Bongard DHJG, Ketelaars M, Buijsen J, Rozema T, Franssen JH, Velema LA, van Triest B, Marijnen CAM. Endorectal Brachytherapy Boost After External Beam Radiation Therapy in Elderly or Medically Inoperable Patients With Rectal Cancer: Primary Outcomes of the Phase 1 HERBERT Study. Int J Radiat Oncol Biol Phys. 2017 Jul 15;98(4):908-917. doi: 10.1016/j.ijrobp.2017.01.033. Epub 2017 Jan 20.
citation: 4. Garcia-Aguilar J, Patil S, Kim JK, et al. Preliminary results of the organ preservation of rectal adenocarcinoma (OPRA) trial. J Clin Oncol 38: 2020 (suppl; abstr 4008).