The aim of the CORRECT phase 2 study is to show non-inferiority of Contact x-ray brachytherapy (CXB) + short-course radiotherapy (SCRT) compared to the experimental arm of the OPERA trial in organ preservation for early and early intermediate rectal cancer (cT1-3abN1).

The primary aim of this study is to determine whether a combination of CXB + SCRT is non-inferior to CXB + chemoradiotherapy (CRT) regarding the primary endpoint 2-year organ preservation rate. Additionally, we hypothesize that a chemotherapy-free, radiation-only experimental treatment CXB+SCRT is associated with less side-effects compared to the OPERA regime.

In the OPERA trial (Gerard et al, 2023), the CXB was delivered in combination with long-course CRT. A combination of short-course radiotherapy (SCRT) and CXB has previously been used mainly in elderly and comorbid patients not suitable for long-course chemoradiotherapy. Recently, an international multi-institution report showed good outcomes of planned organ preservation using SCRT together with contact brachytherapy boost. However, no randomized data on this combination therapy are available. There are further no trials comparing CRT+CXB and SCRT+CXB.

Study participants will be randomized to either the standard treatment consisting of CXB (90Gy/3 fractions/4 weeks) and CRT 45/50 Gy (1.8/2 Gy/fraction/5 weeks) with concurrent chemotherapy using capecitabine (900 mg/m2 bid, on radiation days) OR the experimental treatment consisting of CXB (90Gy/3 fractions/4 weeks) SCRT (25 Gy in 5 daily fractions over a total time of 1 week, treating 5 days per week, 1 fraction per day, using 5 Gy per fraction, over the maximum treatment period of eight calendar days).

Inclusion Criteria:

• Adenocarcinoma of the rectum classified as:
• cT1-cT3ab, < 5 cm largest diameter and < ½ circumference (MRI staging), N0-N1 (<= 3 nodes < 8mm diameter), M0
• Performance status (ECOG) 0-1
• Operable patient
• Tumor accessible to endocavitary contact X-ray brachytherapy with a distance from the lower tumor border to the anal verge ≤10 cm
• 18 years or above
• No comorbidity preventing treatment
• Patient having read the information note and having signed the informed consent
• Follow-up possible

Exclusion Criteria:

• Inoperable patient
• T3cd, T4, T≥ 5cm, Involvement of more than half of the bowel circumference
• Distance from the lower tumor border to the anal verge >10 cm
• N2-status at diagnosis or N1 with any node>= 8 mm diameter
• Patient presenting with metastasis at diagnosis (M1)
• Previous pelvic irradiation
• Tumor with extramural vascular invasion
• Poorly differentiated tumor
• Simultaneous progressive cancer
• Tumor invading external anal sphincter or growth within 1 mm of the levator
• Tumor within 1 mm from MRF (mesorectal fascia)
• Patient unable to receive CXB or CRT
• Any significant concurrent medical illness that in the opinion of the investigator would preclude protocol therapy
• Patient with history of poor compliance or current or past psychiatric conditions or severe acute or chronic medical conditions that would interfere with the ability to comply with the study protocol
• Concurrent enrolment in another clinical trial using an investigational anti-cancer treatment within 28 days prior to the first dose of study treatment
• Total DPD deficiency

Anonymized individual participant data that underlie the reported results.

Beginning 9 months and ending 36 months following article publication.

Researchers who provide a methodologically sound proposal and whose proposed use of the data has been approved by an independent review committee. A data-sharing agreement will also be required. Contact: alexander.valdman@ki.se