Contact Radiotherapy for Rectal Cancer (CORRECT)

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

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).

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Radiation: Radiotherapy; Radiation: Contact x-ray brachytherapy; Drug: Chemotherapy; Radiation: Short-course radiotherapy

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).

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alexander Valdman, MD, PhD; Phone Number: +46 70 002 13 17; Email: alexander.valdman@regionstockholm.se

Study Locations

• Sweden
  • Uppsala, Sweden, 751 85
    • Recruiting
    • Uppsala University Hospital, Colorectal Surgery
    • Contact: Joakim Folkesson, MD, PhD; Phone Number: +46 18 611 00 00; Email: joakim.folkesson@akademiska.se
  • Solna
    • Stockholm, Solna, Sweden, 171 76
      • Recruiting
      • Karolinska University Hospital, Theme Cancer, Dept of Pelvic cancer
      • Contact: Per J Nilsson, MD, PhD; Phone Number: +46 724 69 48 14; Email: per.j.nilsson@regionstockholm.se
      • Principal Investigator: Per J Nilsson, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CXB + CRT; Contact x-ray brachytherapy (CXB) (90Gy/3 fractions/4 weeks) and chemoradiotherapy (CRT) 45/50 Gy (1.8/2 Gy/fraction/5 weeks) with concurrent chemotherapy using capecitabine (900 mg/m2 bid, on radiation days).	Radiation: Radiotherapy; 45/50 Gy (1.8/2 Gy/fraction/5 weeks); Radiation: Contact x-ray brachytherapy; 90Gy/3 fractions/4 weeks; Drug: Chemotherapy; Capecitabine (900 mg/m2 bid, on radiation days)
Experimental: CXB + SCRT; Contact x-ray brachytherapy (CXB) (90Gy/3 fractions/4 weeks) and a short-course radiotherapy (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).	Radiation: Contact x-ray brachytherapy; 90Gy/3 fractions/4 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rectum preservation	Proportion of patients with successful rectum preservation after standard vs experimental treatment. Organ preservation is considered to have failed if the rectum is removed OR if the patient develops non-salvageable locoregional failure	At 24 months after start of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute treatment-related toxicity	Incidence of grade 3-5 toxicity as assessed by CTCAE v5.0	From start of treatment until 90 days after ending treatment
Late treatment related toxicity	Incidence of grade 3-5 toxicity as assessed by CTCAE v5.0	From 90 days after ending treatment until end of study
Clinical complete response (cCR)	Proportion of patients with cCR as assessed by DRE, endoscopy, MRI-T2W, and MRI-DWI	At 14-16 and 24-26 weeks after start of treatment
Postoperative complications	Difference in postoperative complications (graded according to Clavien-Dindo) after standard vs experimental treatment	Within the first 30 days after Total Mesorectal Excision (TME) surgery
Stoma	Proportion of patients with a stoma	At 12 and 24 months after start of treatment
Metastasis-free survival	Survival without sign of metastasis after standard vs experimental treatment	At 24 months after start of treatment
Locoregional failure	Proportion of patients with locoregional failure after standard vs experimental treatment	At 24 months after start of treatment
Overall survival	Overall survival after standard vs experimental treatment	At 24 months after start of treatment
TME-free survival	Survival without Total Mesorectal Excision after standard vs experimental treatment	At 24 months after start of treatment
Salvage TME resections	Rate of R0 Total Mesorectal Excisions after standard vs experimental treatment	From 24 weeks after start of treatment until end of study
Tumor regression grade	Tumor regression grade in the surgical specimen (R0, ypT0, ypTNM) after standard vs experimental treatment	After 14-16 weeks and 24-26 weeks after start of treatment
Sphincter preservation	Rate of sphincter preservation after standard vs experimental treatment	At 24 months after start of treatment
General Health Related Quality of Life (HR QoL)	General Health Related Quality of Life (HR QoL) as measured by the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire QLQ-C30. Responses made on a Likert scale are transformed to a score from 0 to 100 where a higher score indicate a better quality of life	At baseline and at 3, 6, 12, 24, 36, 48 and 60 months after start of treatment
Colorectal cancer specific Health Related Quality of Life (HR QoL)	Health Related Quality of Life (HR QoL) as measured by the European Organisation for Research and Treatment of Cancer (EORTC) colorectal cancer specific quality of life questionnaire QLQ-CR29. Responses made on a Likert scale are transformed to a score from 0 to 100 where a higher score indicate a better quality of life	At baseline and at 3, 6, 12, 24, 36, 48 and 60 months after start of treatment
Bowel function	Bowel function as assessed by the Low Anterior Resection Syndrome (LARS) score. LARS is scored from 0 to 42 points and a higher score indicates worse outcome.	At baseline, 3, 6, 12, 24, 36, 48 and 60 months after start of treatment

Collaborators and Investigators

• Sponsor: Alexander Valdman
• Collaborators: Karolinska Institutet; Uppsala University Hospital

Publications and helpful links

General 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;8(4):356-367. doi: 10.1016/S2468-1253(22)00392-2. Epub 2023 Feb 16.

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2025
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): November 1, 2032

Study Registration Dates

• First Submitted: July 3, 2024
• First Submitted That Met QC Criteria: July 11, 2024
• First Posted (Actual): July 15, 2024

Study Record Updates

• Last Update Posted (Actual): June 6, 2025
• Last Update Submitted That Met QC Criteria: June 3, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: radiotherapy; brachytherapy; organ sparing; nonoperative
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms
• Other Study ID Numbers: CORRECT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual participant data that underlie the reported results.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication.
• IPD Sharing Access Criteria: 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
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No