Rectal brachytherapy boost to try to avoid surgery for low-lying residual rectal cancer after total neoadjuvant therapy

Phase 2 Single-Arm Rectal Cancer Brachytherapy for Patients With Low-Lying Residual Adenocarcinoma After Total Neoadjuvant Therapy to Improve Organ Preservation Rates

This trial will try focal internal radiation (rectal brachytherapy) for people with low-lying residual rectal adenocarcinoma after total neoadjuvant therapy to see if it can produce complete responses and avoid surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 44 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: University of Colorado, Denver (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 3 sites (Aurora, Colorado and 2 other locations)
• Trial ID: NCT07292298 on ClinicalTrials.gov

What this trial studies

Patients with incomplete or near-complete responses after standard total neoadjuvant therapy will undergo pelvic MRI and sigmoidoscopy with marker placement to define residual tumor for planning. A multichannel rectal cylinder is positioned under local analgesia, a balloon is inflated to displace uninvolved rectum, and three weekly outpatient brachytherapy sessions deliver a total of 21 Gy targeted to the high‑risk mucosa at a depth matching tumor thickness. The cylinder may be immobilized for up to three hours during each session while radiation delivery itself takes under ten minutes, and patients who achieve a complete response enter standard nonoperative surveillance with aligned study visits for two years. Although rectal brachytherapy has prior safety and efficacy data from Europe and Canada, this protocol specifically tests its role as a boost after total neoadjuvant therapy in U.S. centers.

Who should consider this trial

Good fit: Adults (18–100 years) with MMR‑proficient low‑to‑mid rectal adenocarcinoma who completed total neoadjuvant therapy but have incomplete or near‑complete residual tumor limited to <4 cm craniocaudal length, <1.2 cm thickness, and <50% circumferential involvement and for whom surgical resection would be an abdominoperineal or low anterior resection.

Not a fit: Patients with a complete clinical response, metastatic disease, tumors exceeding the size or circumferential limits, MMR‑deficient cancers, or those who cannot tolerate the brachytherapy procedure are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, this approach could allow some patients to avoid major rectal surgery and preserve normal bowel function.

How similar studies have performed: Previous studies from Europe and Canada have demonstrated safety and efficacy for rectal brachytherapy, but its use as a post‑neoadjuvant boost has not been widely tested in the United States.

Eligibility criteria

Inclusion Criteria:

1. Provision to sign and date the consent form.
2. Stated willingness to comply with all study procedures and be available for the duration of the study.
3. Adults (18-100 years old)
4. ECOG 0-3
5. Patients with MMR-proficient low-mid rectal adenocarcinoma cT1-4 N0-2 M0 who underwent total neoadjuvant therapy who have not achieved complete response (i.e. incomplete or near-complete) in the rectal primary tumor such that surgical resection, if offered presently or in the future, would be an APR or low LAR per colorectal surgeon expert opinion and central review at University of Colorado rectal tumor board. Tumor restaging will be 4-16 weeks following completion of total neoadjuvant therapy, and no sooner than 8 weeks if patients received chemotherapy followed by chemoradiation/short course radiation.
6. Residual rectal disease must have its craniocaudal extent \<4 cm with thickness \<1.2 cm. Tumor must have \<50% circumferential involvement. Residual disease must be above the dentate line and not involving the anal canal.
7. In patients with original cN1-2 disease, restaging CT and MRI after total neoadjuvant therapy must demonstrate at least near-complete response of the pelvic lymph nodes per NCCN criteria as evaluated by central review at University of Colorado rectal tumor board.
8. Interval of time between completion of TNT and initiation of rectal brachytherapy must be between 4-16 weeks.
9. Patients must be recovered from total neoadjuvant therapy and must not have significant rectal incontinence at time of screening.
10. Received conventionally fractionated external beam chemoradiation between 45-56 Gy or short-course external beam radiation prescription of 25 Gy to rectal mucosa, in addition to systemic chemotherapy before or after radiation per National Comprehensive Cancer Network (NCCN) guidelines.
11. Women of child-bearing potential must have a negative urine or serum pregnancy test within 14 days of HDR treatment.
12. Men and women of reproductive potential who are sexually active must agree to follow instructions of contraception for the duration of the study and 6 months post-rectal brachytherapy completion.
13. CBC at the time of screening must have platelets\>50 10\^9/L, Hemoglobin\>8 g/dL and Absolute Neutrophil Count \> 500 10\^9/L

Exclusion Criteria:

1. History of ulcerative colitis or Crohn's disease.
2. Pelvic radiotherapy given prior to rectal cancer external beam radiation.
3. Prior colorectal surgery in which anastomotic site is at or near HDR brachytherapy target.

   o Prior local excision is not an exclusion criterion.
4. Uncontrolled intercurrent severe illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
5. Life expectancy \<3 years per provider discretion.
6. Concurrent administration of any cytotoxic chemotherapy, immunotherapy, or other any targeted oncologic agent that would impact rectal cancer is not allowed during study protocol.
7. If rectal cancer has been treated outside of standard total neoadjuvant therapy per NCCN guidelines, patients are ineligible for the trial. This includes if patients received external beam chemoradiation dose with prescription \>56 Gy or short-course radiation to rectal mucosa prescription \>30 Gy.
8. Pregnant women.

Where this trial is running

Aurora, Colorado and 2 other locations

• University of Colorado Cancer Center — Aurora, Colorado, United States (Recruiting)
• University of Rochester Medical Center — Rochester, New York, United States (Not_yet_recruiting)
• Oregon Health and Sciences University — Portland, Oregon, United States (Not_yet_recruiting)

Study contacts

• Principal investigator: David Binder — University of Colorado, Denver
• Study coordinator: Radiation Therapy Group

Conditions Rectal Adenocarcinoma; Rectal Cancer; Locally Advanced Rectal Cancer; Non-metastatic Rectal Cancer; Rectal Neoplasms