Chemotherapy followed by high-dose radiation for locally advanced rectal cancer

Selective Treatment With Magnetic Resonance Image Guided Pelvic Adaptive Radiation Therapy Combined With Total Neoadjuvant ChemoTherapy for the Conservative Management of Locally Advanced Rectal Cancer

This study is testing if giving chemotherapy followed by a higher dose of radiation can help people with locally advanced rectal cancer avoid surgery by seeing if it leads to a complete response.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Miami (Academic / other)
• Drugs / interventions: ChemoTherapy, radiation
• Locations: 1 site (Miami, Florida)
• Trial ID: NCT05412082 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and effectiveness of a treatment regimen for patients with locally advanced rectal cancer (LARC) that involves administering chemotherapy first, followed by a higher dose of radiation therapy than typically used. The goal is to determine if this approach can lead to a complete response in patients, potentially allowing them to avoid surgery. The study will utilize intensity-modulated radiation therapy along with specific chemotherapy agents such as 5-fluorouracil, leucovorin, oxaliplatin, and capecitabine. Participants will be closely monitored for their response to treatment and any side effects.

Who should consider this trial

Good fit: Ideal candidates include adults with newly diagnosed, biopsy-proven rectal adenocarcinoma that meets specific tumor staging criteria.

Not a fit: Patients with metastatic disease or those with a history of pelvic radiotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could spare patients from the need for surgery while effectively managing their cancer.

How similar studies have performed: While this approach is innovative, similar studies have shown promise in improving outcomes for rectal cancer patients, suggesting potential for success.

Eligibility criteria

Inclusion Criteria:

1. Patients with newly diagnosed, biopsy proven, rectal adenocarcinoma.
2. Primary tumor located ≤18 cm from margin verge.
3. Primary tumor either a T3N0 or T1-4 N positive (as defined per pelvic MRI; nodes ≤ 15 mm).
4. ≥ 18 years of age.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
6. Serum liver function tests values within the range of 1.5 x Upper Limit of Normal (within 6 weeks of enrollment).
7. Negative pregnancy test for women of child-bearing potential (within 4 weeks of enrollment).
8. Ability to understand and the willingness to sign a written informed consent document.
9. Patient is assessed by a surgeon, medical oncologist and a radiation oncologist and deemed fit for Total Neoadjuvant ChemoTherapy (TNT) and surgery.

Exclusion Criteria:

1. Metastatic disease on initial work up (Chest and abdomen contrast enhanced CT scan).
2. Synchronous cancer found on colonoscopy.
3. Previous history of pelvic radiotherapy.
4. History of concurrent, active malignancy other than non-metastatic skin cancer within the last 2 years.
5. Symptomatic congestive heart failure of New York Heart Association Class III or IV, unstable angina pectoris or uncontrolled severe cardiac arrhythmia, myocardial infarction within the last 6 months.
6. Psychiatric illness/social situations that would limit compliance with study requirements.
7. Active (acute or chronic) or uncontrolled severe infections requiring intravenous antibiotics or active tuberculosis (TB).
8. Patients with poorly controlled acquired immune deficiency syndrome (AIDS) who are not deemed candidates for FOLFOX, mFOLFIRINOX or CAPOX chemotherapy. Active connective tissue disorders, such as lupus or scleroderma, that, in the opinion of the treating physician may put the patient at high risk for radiation toxicity.
9. Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity
10. Sensory or motor neuropathy ≥ grade 2.
11. Women who are breast feeding.
12. Exclusions due to MRI use in study: ferromagnetic metal in body/eye, pacemaker, defibrillator, other mechanical device, or extreme claustrophobia (medication with anti-anxiety agents, such as Ativan, may be attempted).

Where this trial is running

Miami, Florida

• University of Miami — Miami, Florida, United States (Recruiting)

Study contacts

• Principal investigator: Benjamin Spieler, MD — University of Miami
• Study coordinator: Zuzel Rodriguez

Conditions Locally Advanced Rectal Cancer