NCT05412082 · University of Miami
SMART TNT for the Conservative Management of Locally Advanced Rectal Cancer
(SMART TNT)
What this study is about
The purpose of this research study is to find out how safe and effective is treating patients with locally advanced rectal cancer (LARC) with chemotherapy first and then follow with radiation therapy to a higher dose than what is usually delivered and see if patients could have full disappearance of disease signs and be spared from surgery.
View original scientific description
The purpose of this research study is to find out how safe and effective is treating patients with locally advanced rectal cancer (LARC) with chemotherapy first and then follow with radiation therapy to a higher dose than what is usually delivered and see if patients could have complete response and be spared from surgery.
Interventions
RADIATION
Intensity-modulated radiation therapy
MRI-guided pelvic IMRT to the Planning Tumor Volume (PTV) at a dose of 50 Grays (gy) delivered in 25 fractions (fx) over 5 weeks.
DRUG
5-fluorouracil
5-FU dose of 400 mg/m2 will be administered intravenously (IV) over 5-15 minutes beginning on Day 1; then a dose of 2400 mg/m2 via continual infusion (CI) over 4446-478 hours total dose during Days 1 and 2 of every 14-day cycle, for 4 to 6 cycles. During SMART TNT Plan I, 5-FU dose of 225 mg/m2 per day will be administered via CI on Day 1 radiation therapy, delivered either 5 or 7 days per week.
DRUG
Leucovorin
Leucovorin dose of 400 mg/m2 bolus will be administered intravenously (IV) on Day 1 of each 14-day cycle for 4 to 6 cycles, prior to SMART TNT Plan I radiation therapy.
DRUG
Oxaliplatin
Oxaliplatin dose of 85 mg/m2 will be administered intravenously (IV) on Day 1 of each 14-day cycle for 4 - 6 cycles.
DRUG
Capecitabine
Capecitabine will be administered orally at a dose of 825 mg/m2 via tablet twice per day (BID) on Day 1, 5 days per week.
RADIATION
Accelerated Radiation Therapy
MRI-guided Pelvic accelerated radiation therapy (ART) given over one week at one of the following dose levels : * Dose level -1: 10 Gy delivered in 4 fractions * Dose level 0: 12 Gy delivered in 4 fractions * Dose level 1: 14 Gy delivered in 4 fractions * Dose level 2: 16 Gy in delivered 4 fractions
DRUG
Irinotecan
Irinotecan dose of 180 mg/m2 will be administered intravenously (IV) on Day 1 of each 14-day cycle for 4 to 6 cycles, prior to SMART TNT Plan I radiation therapy.
Primary outcome measures
Incidence of Toxicity Among Participants After Start Receiving MRI-g Pelvic ART
Time frame: Up to 30 months
Reported as the incidence of toxicity (adverse events and serious adverse events) in study participants after start of MRI-g Pelvic ART. Toxicity in study participants will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Patients with newly diagnosed, biopsy proven, rectal adenocarcinoma.
- Primary tumor located ≤18 cm from margin verge.
- Primary tumor either a T3N0 or T1-4 N positive (as defined per pelvic MRI; nodes ≤ 15 mm).
- ≥ 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Serum liver function tests values within the range of 1.5 x Upper Limit of Normal (within 6 weeks of enrollment).
- Negative pregnancy test for women of child-bearing potential (within 4 weeks of enrollment).
- Ability to understand and the willingness to sign a written informed consent document.
- Patient is assessed by a surgeon, medical oncologist and a radiation oncologist and deemed fit for Total Neoadjuvant ChemoTherapy (TNT) and surgery.
Exclusion criteria
- Metastatic disease on initial work up (Chest and abdomen contrast enhanced CT scan).
- Synchronous cancer found on colonoscopy.
- Previous history of pelvic radiotherapy.
- History of concurrent, active malignancy other than non-metastatic skin cancer within the last 2 years.
- 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.
- Psychiatric illness/social situations that would limit compliance with study requirements.
- Active (acute or chronic) or uncontrolled severe infections requiring intravenous antibiotics or active tuberculosis (TB).
- 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.
- 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
- Sensory or motor neuropathy ≥ grade 2.
- Women who are breast feeding.
Where
- Miami, Florida
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Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Feb 6, 2026 · Source of record for eligibility and locations