Brachytherapy Followed by Nivolumab Prior to Surgery in Rectal Cancer

NCT07645118 | Not Yet Recruiting Phase 2

• 1 other identifier: IMPERIA-01
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is a small Phase II study testing whether targeted internal radiation treatment (HDREBT) followed by two doses of the immunotherapy drug Nivolumab is safe, practical, and potentially effective before patients undergo surgery (TME) to remove rectal cancer.

Conditions

Locally Advanced Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response (pCR)

  This is assessed at the time of total mesorectal excision surgery, occurring approximately 12 weeks after enrollment.

Secondary Outcomes (2)

• Incidence and severity of adverse events, as per CTCAE criteria v6.0

  From time of first treatment through 90 days following last treatment with nivolumab

• Assess feasibility of treatment sequence

  This is assessed from the time of enrollment until the time of surgery, approximately 12 weeks after enrolment.

Study Arms (1)

Brachytherapy (HDREBT) followed by nivolumab and total mesorectal excision

EXPERIMENTAL

HDREBT (26 Gy delivered in 4 fractions over Days 1-4) followed by up to 2 doses of nivolumab (3 mg/kg mg IV every 2 weeks starting at 7-14 days post HDREBT). Surgical resection of tumor (6-8 weeks post HDREBT)

Drug: Nivolumab; Device: HDRBET; Procedure: Total Mesorectal Excision (TME)

Interventions

Nivolumab DRUG

2 doses of nivolumab 3 mg/kg mg IV every 2 weeks

Brachytherapy (HDREBT) followed by nivolumab and total mesorectal excision

HDRBET DEVICE

26 Gy in 4 fractions Administered over Days 1-4 as per institutional standard

Brachytherapy (HDREBT) followed by nivolumab and total mesorectal excision

Total Mesorectal Excision (TME) PROCEDURE

Targeted to take place 6-8 weeks post completion of HDREBT (maximum 12 weeks)

Brachytherapy (HDREBT) followed by nivolumab and total mesorectal excision

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years at the time of consent.
• Histologically confirmed rectal adenocarcinoma arising within 5 to 15 cm of the anal verge as measured by sigmoidoscopy or MRI.
• Rectal cancer staging:
• Clinical Stage cT2 or cT3 based on high resolution pelvic MRI;
• No evidence of distant metastases (cM0) on contrast -enhanced CT of chest, abdomen and pelvis (or PET/CT if clinically indicated);
• Disease deemed technically resectable with curative intent by multidisciplinary tumor board (MDT)\*. No radiologic evidence of unresectable local disease (e.g., tumor fixation or invasion of adjacent unresectable structures).
• At least one of the following adverse prognostic features observed on baseline MRI:
• Node-positive disease (cN+);
• Threatened mesorectal fascia (MRF) defined as distance from tumor to mesorectal fascia \< 1mm on pelvic MRI;
• Extramural venous invasion (EMVI+).
• Proficient mismatch repair (pMMR) status, as determined by immunohistochemistry and/or microsatellite instability-low (MSI-L) status by next-generation sequencing
• Planned management includes neoadjuvant therapy with radiotherapy followed by curative-intent TME.
• Prior external beam pelvic radiation for other malignancy (prostate, gynecology, lymphoma, bladder) are acceptable, provided the colorectal surgeon deems the patient as a candidate for TME surgery.
• ECOG performance status of 0-2
• Adequate organ function, defined by:

You may not qualify if:

• Prior anticancer therapy for rectal cancer.
• Contraindication to safe MRI imaging.
• Evidence of bowel obstruction on MRI or clinical evaluation.
• Evidence of distant metastasis.
• Medical or surgical contraindications to major pelvic surgery
• Active autoimmune disease requiring systemic immunosuppressive therapy.
• Active/uncontrolled infection. Infectious screening for HIV, Hepatitis B (HBV), Hepatitis C (HBC) and tuberculosis will be performed at screening:
• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received HBV anti-viral therapy for at least 4 weeks; and have undetectable HBV viral load prior to starting treatment. Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.
• Participants with a history of HCV infection are eligible if HCV viral load is undetectable at screening. Note: Participants must have completed curative anti-viral therapy at least 4 weeks prior to start of treatment.
• HIV-infected participants must have well-controlled HIV on antiretroviral treatment (ART), defined as:
• i. have a CD4+ T-cell count ≥ 0.35 x109 cells/L at the time of screening. ii. must have achieved and maintained virologic suppression defined as confirmed HIV ribonucleic acid (RNA) level below 50 or the LLOQ (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening.
• iii. must not have had any AIDS-defining opportunistic infections within the past 12 months.
• iv. must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before start of treatment and agree to continue ART throughout the study.
• Known allergy or hypersensitivity to nivolumab or any of its excipients.
• Patients with other psychiatric, social or severe or uncontrolled medical conditions that in the opinion of the investigator may compromise their compliance with the protocol or may represent an unacceptable risk to their safety (e.g. uncontrolled diabetes, active or uncontrolled infection, uncontrolled clinically significant cardiovascular disease).

Sponsors & Collaborators

• Dr. Te Vuong: lead

Study Sites (1)

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Related Publications (2)

• Vuong T, Devic S, Podgorsak E. High dose rate endorectal brachytherapy as a neoadjuvant treatment for patients with resectable rectal cancer. Clin Oncol (R Coll Radiol). 2007 Nov;19(9):701-5. doi: 10.1016/j.clon.2007.07.006. Epub 2007 Aug 22.

  PMID: 17714925 BACKGROUND

• Lin ZY, Zhang P, Chi P, Xiao Y, Xu XM, Zhang AM, Qiu XF, Wu JX, Yuan Y, Wang ZN, Qu XJ, Li X, Nie X, Yang M, Cai KL, Zhang WK, Huang Y, Sun Z, Hou ZG, Ma C, Cheng FZ, Tao KX, Zhang T. Neoadjuvant short-course radiotherapy followed by camrelizumab and chemotherapy in locally advanced rectal cancer (UNION): early outcomes of a multicenter randomized phase III trial. Ann Oncol. 2024 Oct;35(10):882-891. doi: 10.1016/j.annonc.2024.06.015. Epub 2024 Jul 2.

  PMID: 38964714 BACKGROUND

MeSH Terms

Interventions

Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor Oncology, Radiation Oncologist, McGill University

Study Record Dates

• First Submitted: June 2, 2026
• First Posted: June 12, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2030
• Last Updated: June 12, 2026

Record last verified: 2026-06

Locations

CA (1)