Clinical trial NCT06501053: Contact Radiotherapy for Rectal Cancer
Official title: Contact Radiotherapy for Rectal Cancer (CORRECT): a Multicenter Randomized Phase II Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Rectal Cancer
Keywords: organ sparing
brachytherapy
radiotherapy
nonoperative
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
Collaborators: name: Uppsala University Hospital
name: Karolinska Institutet
First posted: 2024-07-15
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Rectum preservation
timeFrame: At 24 months after start of treatment
Secondary outcomes:
measure: Acute treatment-related toxicity
timeFrame: From start of treatment until 90 days after ending treatment
measure: Late treatment related toxicity
timeFrame: From 90 days after ending treatment until end of study
measure: Clinical complete response (cCR)
timeFrame: At 14-16 and 24-26 weeks after start of treatment
measure: Postoperative complications
timeFrame: Within the first 30 days after Total Mesorectal Excision (TME) surgery
measure: Stoma
timeFrame: At 12 and 24 months after start of treatment
measure: Metastasis-free survival
timeFrame: At 24 months after start of treatment
measure: Locoregional failure
timeFrame: At 24 months after start of treatment
measure: Overall survival
timeFrame: At 24 months after start of treatment
measure: TME-free survival
timeFrame: At 24 months after start of treatment
measure: Salvage TME resections
timeFrame: From 24 weeks after start of treatment until end of study
measure: Tumor regression grade
timeFrame: After 14-16 weeks and 24-26 weeks after start of treatment
measure: Sphincter preservation
timeFrame: At 24 months after start of treatment
measure: General Health Related Quality of Life (HR QoL)
timeFrame: At baseline and at 3, 6, 12, 24, 36, 48 and 60 months after start of treatment
measure: Colorectal cancer specific Health Related Quality of Life (HR QoL)
timeFrame: At baseline and at 3, 6, 12, 24, 36, 48 and 60 months after start of treatment
measure: Bowel function
timeFrame: At baseline, 3, 6, 12, 24, 36, 48 and 60 months after start of treatment
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Karolinska University Hospital, Theme Cancer, Dept of Pelvic cancer
state: Solna
city: Uppsala
country: Sweden
facility: Uppsala University Hospital, Colorectal Surgery
Study officials:
References:
citation: 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.