Contact Radiotherapy for Rectal Cancer

Official title

Contact Radiotherapy for Rectal Cancer (CORRECT): a Multicenter Randomized Phase II Trial

Overview

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).

Detailed description

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).

Interventions

• Radiation Radiotherapy
  45/50 Gy (1.8/2 Gy/fraction/5 weeks)
• Radiation Short-course radiotherapy
  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
• Radiation Contact x-ray brachytherapy
  90Gy/3 fractions/4 weeks
• Drug Chemotherapy
  Capecitabine (900 mg/m2 bid, on radiation days)

Primary outcome measures

• Rectum preservation [Time frame: At 24 months after start of treatment]

Secondary outcome measures (12)

• Acute treatment-related toxicity [Time frame: From start of treatment until 90 days after ending treatment]
• Late treatment related toxicity [Time frame: From 90 days after ending treatment until end of study]
• Clinical complete response (cCR) [Time frame: At 14-16 and 24-26 weeks after start of treatment]
• Postoperative complications [Time frame: Within the first 30 days after Total Mesorectal Excision (TME) surgery]
• Stoma [Time frame: At 12 and 24 months after start of treatment]
• Metastasis-free survival [Time frame: At 24 months after start of treatment]
• Locoregional failure [Time frame: At 24 months after start of treatment]
• Overall survival [Time frame: At 24 months after start of treatment]
• TME-free survival [Time frame: At 24 months after start of treatment]
• Salvage TME resections [Time frame: From 24 weeks after start of treatment until end of study]
• Tumor regression grade [Time frame: After 14-16 weeks and 24-26 weeks after start of treatment]
• Sphincter preservation [Time frame: At 24 months after start of treatment]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Sweden · 2 centers

• Karolinska University Hospital, Theme Cancer, Dept of Pelvic cancer — Stockholm
• Uppsala University Hospital, Colorectal Surgery — Uppsala

Publications

• 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 PMID 36801007
• Nilsson PJ, Folkesson J, Marsk R, Radu C, Stratulat I, Blomqvist L, Martling A, Valdman A. Contact radiotherapy for rectal cancer (CORRECT): study protocol for a multicentre randomised phase II trial. BMJ Open. 2025 Apr 9;15(4):e100356. doi: 10.1136/bmjopen-2025-100356. PMID 40204311

Identifiers

NCT: NCT06501053 · CORRECT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗