Organ Preservation in Rectal AdenoCa Using Hypofractionated Pelvic RT(Hypo-OPRA)

Phase 2

Recruiting

• Conditions: Colorectal Carcinoma
• Interventions: Radiation: Radiation Therapy; Drug: FOLFOX regimen; Drug: Capecitabine

• Registration Number: NCT06991465
• Lead Sponsor: Neil Kopek

Brief Summary

The combination of preoperative pelvic RT - either long-course chemoradiotherapy (LCCRT) or short-course radiotherapy (SCRT)- followed by surgery has been the standard of care in the curative treatment of locally advanced adenocarcinoma of the rectum for decades. Some patients however achieve a complete clinical response (cCR) to their preoperative treatment which opens the possibility of avoiding surgery and consequently preserving the rectum. There now exists a growing body of data from centres around the world validating the safety of a surveillance approach in clinical complete responders treated with LCCRT.

Detailed Description

At McGill, SCRT is used routinely as a pre-operative radiotherapy schedule for locally advanced adenocarcinomas of the rectum. Likewise SCRT followed by chemotherapy is already used routinely at McGill as a pre-operative regimen for locally advanced rectal cancer with high risk features. Compelling registry data from Scandinavia shows that enduring clinical complete responses can be achieved after SCRT. To date, however, nearly all of the published data supporting a surveillance strategy in complete clinical responders is based on LCCRT. The present study proposes to explore further the organ preservation potential of SCRT.

Adopting a non-operative strategy in rectal cancer patients who achieve complete tumour regression avoids the risks of surgical morbidity and mortality, notably a sparing of the rectal sphincter muscles in the case of low-lying tumours and consequently avoidance of a permanent stoma.

Although multiple phase III trials support the routine use of SCRT in the pre-operative setting for locally advanced rectal adenocarcinoma, to date nearly all of the published data supporting a surveillance strategy in complete clinical responders is based on LCCRT. Compelling registry data from Scandinavia does show that enduring clinical complete responses can be achieved after short-course pelvic radiotherapy. Furthermore, the Rectal Cancer and Pre-operative Induction Therapy Followed by Dedicated Operation (RAPIDO) study demonstrated that, compared with LCCRT, SCRT followed by chemotherapy (SCRT-CH) has a higher pathologic complete response rate (29% versus 14%), less disease-related treatment failure, and superior distant metastasis-free survival.

Short-course pelvic radiotherapy with or without sequential chemotherapy can induce enduring clinical complete responders and the use of SCRT as part of a non-operative organ preservation strategy merits further prospective exploration. At McGill, SCRT is already used routinely as a pre-operative dose schedule for clinically node negative/N1 locally advanced adenocarcinomas of the rectum where downsizing is not required to achieve a sphincter sparing R0 resection. Likewise, since the publication of the RAPIDO trial, SCRT followed by FOLFOX/CAPOX chemotherapy has emerged as the preferred regimen at McGill for patients with high risk features (cT4 disease, cN2 and/or extramesorectal nodes, EMVI+, threatened or involved mesorectal fascia and/or sphincter muscles). The present phase II prospective study proposes to explore further the organ preservation potential of SCRT combined with a simultaneous integrated boost on sites of gross disease..

Study Timeline

• Study Start: 2023-08-16
• Status Verified: 2025-05
• Study First Submitted: 2025-05-12
• Study First Submitted QC: 2025-05-23
• Last Update Submitted: 2025-05-23
• Study First Posted: 2025-05-28
• Last Update Posted: 2025-05-28
• Primary Completion: 2027-09
• Study Completion: 2029-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

• Histologically confirmed invasive adenocarcinoma of the rectum
• Pelvic MRI defined disease (at least one of the following):

mesorectum involved or breached - includes involvement of adjacent organ(s) (T3-T4)

• Patients are considered medically fit for oncologic resection
• ECOG performance status 0 or 1
• No evidence of established metastatic disease (CT chest and abdomen)
• Absolute neutrophil count >1.5x109/L; platelets >100x109/L,
• Serum transaminase <3 x ULN;
• Adequate renal function (Cockroft Gault estimation >50 mL/min)
• Bilirubin <1.5 x ULN
• Ability to comply with oral medication
• Willingness and ability to give informed consent and comply with treatment and follow up schedule
• Age 18 or over

Exclusion Criteria

• Previous chemotherapy
• Previous radiotherapy to the pelvis (including brachytherapy)
• Uncontrolled cardiorespiratory comorbidity (includes patients with inadequately controlled angina or myocardial infarction within 6 months of randomisation)
• T1 or T2 N0 disease without extra-mural venous invasion
• Unequivocal evidence of metastatic disease (includes resectable metastases)
• Major impairment of bowel function without defunctioning stoma/ileostomy (baseline grade 3 diarrhoea or clinically significant faecal incontinence
• Known dihydropyrimidine dehydrogenase deficiency
• History of another malignancy within the last 5 years except successfully treated basal cell cancer of skin or carcinoma in situ of uterine cervix.
• Known Gilberts disease (hyperbilirubinaemia)
• Taking warfarin or phenytoin or sorivudine
• Gastrointestinal disorder which would interfere with oral therapy and its bioavailability
• Pregnant, lactating, or pre-menopausal women not using adequate contraception
• Unfit to receive any study treatment or subsequent surgical resection

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Hypofractionated Pelvic Radiotherapy	Radiation Therapy	A single arm consisting of hypofractionated RT dose of 25 Gy in 5 fractions once daily fractions of intensity modulated radiotherapy (IMRT) with a simultaneous integrated boost up to 35 Gy on sites of gross disease (tumour and lymphadenopathy).
Hypofractionated Pelvic Radiotherapy	FOLFOX regimen	A single arm consisting of hypofractionated RT dose of 25 Gy in 5 fractions once daily fractions of intensity modulated radiotherapy (IMRT) with a simultaneous integrated boost up to 35 Gy on sites of gross disease (tumour and lymphadenopathy).
Hypofractionated Pelvic Radiotherapy	Capecitabine	A single arm consisting of hypofractionated RT dose of 25 Gy in 5 fractions once daily fractions of intensity modulated radiotherapy (IMRT) with a simultaneous integrated boost up to 35 Gy on sites of gross disease (tumour and lymphadenopathy).

Primary Outcome Measures

Name	Time	Method
Feasibility of Hypo-fractionated Approach in 5 fractions for a dose of 35Gy	One year	Rate of failure to achieve CR or the rate of recurrence after achieving CR

Trial Locations

Locations (1)

McGill University Health Centre; 🇨🇦 Montreal, Quebec, Canada