Adaptive radiation boost to try to preserve the rectum in people with rectal adenocarcinoma

Adaptive Radiation BOost for Rectal Cancer: a Phase I Dose Escalation Study (ARBOR)

This trial tries adding an MRI-guided adaptive radiation boost after standard chemoradiation for adults with localized rectal adenocarcinoma to better target tumor cells and spare healthy tissue.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 37 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fox Chase Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT07221058 on ClinicalTrials.gov

What this trial studies

This Phase 1 interventional protocol gives standard long-course chemoradiation (45 Gy in 25 fractions with concurrent capecitabine) followed by an adaptive radiation boost guided by repeat MRI scans every two weeks. During boost treatments an intrarectal balloon is used to stabilize and protect nearby tissue while the boost plan is modified based on tumor response. After radiation, patients receive additional systemic chemotherapy such as FOLFOX for about four months. The primary aim is to determine the safety and feasibility of MRI-guided adaptive boosting and its ability to concentrate dose on residual tumor while reducing exposure to normal organs.

Who should consider this trial

Good fit: Adults (≥18) with biopsy-proven rectal adenocarcinoma staged T2-3, N0-1, M0 who can undergo MRI, tolerate capecitabine and subsequent FOLFOX (or equivalent), have ECOG 0–1, and meet baseline blood-count and organ-function requirements.

Not a fit: Patients with metastatic disease, T4 tumors, prior pelvic radiation, inability to undergo MRI, or who cannot tolerate the required chemotherapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could improve tumor control and increase chances of preserving the rectum while reducing radiation-related side effects.

How similar studies have performed: Dose-escalation and MRI-guided adaptive radiotherapy approaches have shown promising responses and organ-preservation signals in prior work, but this specific intrarectal-balloon MRI-adaptive boost strategy is novel and being tested for safety in a Phase 1 setting.

Eligibility criteria

Inclusion Criteria:

1. Subjects must have histologically or cytologically confirmed rectal adenocarcinoma.
2. Subjects must have T2-3, N0-1, M0 rectal cancer. Staging will be done by MRI pelvis and CT chest and abdomen with contrast. PET-CT will be an acceptable alternative for the CT chest and abdomen.
3. Subjects must be willing to undergo MRI scans.
4. Age ≥18 years.
5. ECOG performance status 0 or 1.
6. Estimated survival of ≥ 12 months.
7. Subjects must have normal organ and marrow function as defined below

   * Absolute neutrophil count \> =1,000/mcL
   * Platelets \>= 75,000/mcL
   * Total bilirubin \< 3 mg/dL
8. Subjects must be able to tolerate the chemotherapy regimens outlined in the treatment plan (Section 5.0), both before and after ART.

   * Before ART: Capecitabine at a dose of 825 mg/m²
   * After ART: FOLFOX combination chemotherapy, or 5-FU, or capecitabine
9. Subjects must possess the ability to understand and willingness to sign a written informed consent and HIPAA consent document. Translation services including translation of informed consent documents will be provided, as feasible, to encourage diversity of inclusion of eligible patients.

Exclusion Criteria:

1. Subjects who have been previously treated for rectal cancer are excluded.
2. Subjects with rectal cancer involving the anal canal are excluded. (Rectal cancer abutting the anal canal will be allowed.)
3. Subjects must not be receiving any other investigational agents.
4. Subjects may not have had prior pelvic radiation.
5. Subjects should not have had a cancer actively treated within the last 3 years, excluding non-melanoma skin cancer.
6. Subjects must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
7. Any condition or significant co-morbidity that prevents safe delivery of ART per the discretion of the treating physician(s).
8. Subjects must not be pregnant or breast-feeding.

Where this trial is running

Philadelphia, Pennsylvania

• Fox Chase Cancer Center — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Joshua Meyer — Fox Chase Cancer Center
• Study coordinator: Joshua Meyer, MD

Conditions Rectum Cancer, Adenocarcinoma; Adaptive Radiation Therapy; Rectum Cancer; Adenocarcinoma; Organ Preservation; Total Mesorectal Excision