Rectal Cancer
Conditions
Keywords
organ sparing, brachytherapy, radiotherapy, nonoperative
Brief summary
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
RADIATIONRadiotherapy
45/50 Gy (1.8/2 Gy/fraction/5 weeks)
RADIATIONShort-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
RADIATIONContact x-ray brachytherapy
90Gy/3 fractions/4 weeks
DRUGChemotherapy
Capecitabine (900 mg/m2 bid, on radiation days)
Sponsors
Alexander Valdman
Uppsala University Hospital
Karolinska Institutet
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rectum preservation | At 24 months after start of treatment | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute treatment-related toxicity | From start of treatment until 90 days after ending treatment | Incidence of grade 3-5 toxicity as assessed by CTCAE v5.0 |
| Late treatment related toxicity | From 90 days after ending treatment until end of study | Incidence of grade 3-5 toxicity as assessed by CTCAE v5.0 |
| Clinical complete response (cCR) | At 14-16 and 24-26 weeks after start of treatment | Proportion of patients with cCR as assessed by DRE, endoscopy, MRI-T2W, and MRI-DWI |
| Postoperative complications | Within the first 30 days after Total Mesorectal Excision (TME) surgery | Difference in postoperative complications (graded according to Clavien-Dindo) after standard vs experimental treatment |
| Stoma | At 12 and 24 months after start of treatment | Proportion of patients with a stoma |
| Metastasis-free survival | At 24 months after start of treatment | Survival without sign of metastasis after standard vs experimental treatment |
| Locoregional failure | At 24 months after start of treatment | Proportion of patients with locoregional failure after standard vs experimental treatment |
| Overall survival | At 24 months after start of treatment | Overall survival after standard vs experimental treatment |
| TME-free survival | At 24 months after start of treatment | Survival without Total Mesorectal Excision after standard vs experimental treatment |
| Salvage TME resections | From 24 weeks after start of treatment until end of study | Rate of R0 Total Mesorectal Excisions after standard vs experimental treatment |
| Tumor regression grade | After 14-16 weeks and 24-26 weeks after start of treatment | Tumor regression grade in the surgical specimen (R0, ypT0, ypTNM) after standard vs experimental treatment |
| Sphincter preservation | At 24 months after start of treatment | Rate of sphincter preservation after standard vs experimental treatment |
| General Health Related Quality of Life (HR QoL) | At baseline and at 3, 6, 12, 24, 36, 48 and 60 months after start of treatment | 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 |
| Colorectal cancer specific Health Related Quality of Life (HR QoL) | At baseline and at 3, 6, 12, 24, 36, 48 and 60 months after start of treatment | 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 |
| Bowel function | At baseline, 3, 6, 12, 24, 36, 48 and 60 months after start of treatment | 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. |
Countries
Sweden
Contacts
CONTACTAlexander Valdman, MD, PhD
Outcome results
None listed