Locally Advanced Rectal CancerPhase 1SMART TNTNCT05412082
SMART TNT for the Conservative Management of Locally Advanced Rectal Cancer
A Phase 1 study testing Intensity-modulated radiation therapy, 5-fluorouracil and Leucovorin in people with Locally Advanced Rectal Cancer, run by University of Miami at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Rectal Cancer
- What is being tested?
- Intensity-modulated radiation therapy, 5-fluorouracil and Leucovorin
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Oct 2022to 31 Oct 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
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- 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.
- 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Miami
Miami, Florida, 33136
Zuzel Rodriguez, 305-243-0124, z.rodriguez1@med.miami.edu
Benjamin Spieler, MD, 305-243-4229, bspieler@miami.edu
About this study
Official title: 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
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.
- Conditions
- Locally Advanced Rectal Cancer
- Being tested
- Intensity-modulated radiation therapy, 5-fluorouracil, Leucovorin, Oxaliplatin, Capecitabine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intensity-modulated radiation therapyRadiation
Also called IMRT
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.
5-fluorouracilDrug
Also called 5-FU
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.
LeucovorinDrug
Also called Folinic acid
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.
OxaliplatinDrug
Also called Eloxatin
Oxaliplatin dose of 85 mg/m2 will be administered intravenously (IV) on Day 1 of each 14-day cycle for 4 - 6 cycles.
CapecitabineDrug
Also called Xeloda
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.
Accelerated Radiation TherapyRadiation
Also called ART
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
IrinotecanDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| SMART TNT Plan I | Experimental | Participants will initiate therapy with neoadjuvant chemotherapy of either six (6) 14-day cycles of 5-fluorouracil + leucovorin + oxaliplatin (FOLFOX), six (6) 14-day cycles of 5-fluorouracil + leucovorin + irinotecan + oxaliplatin (mFOLFIRINOX), or four (4) 21-day cycles of capecitabine+oxaliplatin (CAPOX). Participants will then receive chemo-radiation therapy according to Plan I as follows:
Plan I (5 weeks):
* 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.
* Concurrent chemotherapy beginning on Day 1 of RT either:
* 5-FU delivered 5 or 7 days per week.
* Capecitabine (Xeloda) delivered 5 days per week.
After completing Plan I, participants achieving complete Clinical Response (cCR) after completing Plan I chemo-radiation will forgo the Plan II boost and continue to follow-up. Participants not achieving cCR will begin Plan II, one week after completing Plan I. Receives: Radiation: Intensity-modulated radiation therapy; Drug: 5-fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Irinotecan |
| SMART TNT Plan II | Experimental | Plan II boost RT (1 week): For participants not achieving cCR after chemo-radiation. Participants will receive MRI-guided accelerated radiation therapy (ART) boost to the primary tumor.
Participants achieving a cCR will continue to follow-up. Participants still showing residual tumor will undergo standard of care treatment including surgery and adjuvant chemotherapy per institutional guidelines during follow-up. Receives: Radiation: Accelerated Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Toxicity Among Participants After Start Receiving MRI-g Pelvic ART
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.
Measured: Up to 30 months
Secondary outcomes (8)
Incidence of Acute and Long-Term Toxicity After Start of Study Therapy
Reported as the incidence of grade 3 or higher acute and long-term toxicity by organ in study participants after start of study therapy. These toxicities will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.
Measured: Up to 30 months
Percentage of Participants with Documented Local Control
Local control is defined as the stopping of cancer growth at the original primary site. The percentage of participants with documented local control after study therapy will be reported.
Measured: Up to 2 years
Percentage of Participants with Documented Distant Metastasis
Distant metastasis is defined as cancer that has spread form the original (primary) tumor to distant organs and distant lymph nodes. The percentage of participants with documented distant metastasis after study therapy will be reported.
Measured: Up to 2 years
Disease-free Survival (DFS) rate
Disease-free survival is defined as the elapsed time after treatment that a person with disease lives without known disease recurrence. DFS rate will be reported as the percentage of participants without disease recurrence after start of treatment.
Measured: Up to 2 years
Overall Survival (OS)
OS will be reported as the number of participants still alive after start of treatment.
Measured: Up to 2 years
Percentage of Real Negatives
The sensitivity and specificity of multiparametric magnetic resonance imaging (mpMRI) to measure tumor response will be reported as the percentage of real negatives during the course of treatment of study participants.
Measured: Up to 6 months
Health-related Quality of Life (HRQOL) Scores: Patient-Reported Outcomes Measurement Information System (PROMIS)
Patient-Reported Outcomes (PRO) will be measured using the 29-item NIH PROMIS questionnaire, a validated HRQOL measure that provides global levels of health-related quality of life. PROMIS has subscales of emotional distress, fatigue, pain, physical function, sleep disturbance, and satisfaction with social participation.
Measured: Up to 30 months
Health-related Quality of Life (HRQOL) Scores: Pittsburgh Sleep Quality Index (PSQI)
Health-related quality of life will be reported using Pittsburgh Sleep Quality Index (PSQI) which assesses patient-reported sleep quality over a 1-month time interval. The PSQI consists of 19 items including 7 sleep components (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction) that produce one global score. Each item is weighted on a 0-3 interval scale. The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality.
Measured: Up to 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2022
- Study start5 Oct 2022
- Primary completion31 Oct 2026 (estimated)
- Study completion31 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Rectal CancerStudies of the same condition, open and under way.
- More trials run by University of MiamiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Benjamin Spieler, University of Miami
- Investigators
- Benjamin Spieler, MD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05412082
- Sponsor's protocol ID
- 20210172
- Acronym
- SMART TNT
- Status last verified
- Feb 2026
- First submitted
- 6 Jun 2022
- Last updated
- 6 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05412082
- Acronym / sponsor ID
- SMART TNT / 20210172
- Conditions
- Locally Advanced Rectal Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Study start
- 5 Oct 2022 (actual)
- Primary completion
- 31 Oct 2026 (estimated)
- Study completion
- 31 Oct 2028 (estimated)
- First posted
- 9 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SMART TNT Plan I | Experimental | Radiation: Intensity-modulated radiation therapy, Drug: 5-fluorouracil, Drug: Leucovorin, Drug: Oxaliplatin, Drug: Capecitabine, Drug: IrinotecanParticipants will initiate therapy with neoadjuvant chemotherapy of either six (6) 14-day cycles of 5-fluorouracil + leucovorin + oxaliplatin (FOLFOX), six (6) 14-day cycles of 5-fluorouracil + leucovorin + irinotecan + oxaliplatin (mFOLFIRINOX), or four (4) 21-day cycles of capecitabine+oxaliplatin (CAPOX). Participants will then receive chemo-radiation therapy according to Plan I as follows: Plan I (5 weeks): * 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. * Concurrent chemotherapy beginning on Day 1 of RT either: * 5-FU delivered 5 or 7 days per week. * Capecitabine (Xeloda) delivered 5 days per week. After completing Plan I, participants achieving complete Clinical Response (cCR) after completing Plan I chemo-radiation will forgo the Plan II boost and continue to follow-up. Participants not achieving cCR will begin Plan II, one week after completing Plan I. |
| SMART TNT Plan II | Experimental | Radiation: Accelerated Radiation TherapyPlan II boost RT (1 week): For participants not achieving cCR after chemo-radiation. Participants will receive MRI-guided accelerated radiation therapy (ART) boost to the primary tumor. Participants achieving a cCR will continue to follow-up. Participants still showing residual tumor will undergo standard of care treatment including surgery and adjuvant chemotherapy per institutional guidelines during follow-up. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intensity-modulated radiation therapyAlso: IMRTMRI-guided pelvic IMRT to the Planning Tumor Volume (PTV) at a dose of 50 Grays (gy) delivered in 25 fractions (fx) over 5 weeks. | Radiation | SMART TNT Plan I |
| 5-fluorouracilAlso: 5-FU5-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 | SMART TNT Plan I |
| LeucovorinAlso: Folinic acidLeucovorin 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 | SMART TNT Plan I |
| OxaliplatinAlso: EloxatinOxaliplatin dose of 85 mg/m2 will be administered intravenously (IV) on Day 1 of each 14-day cycle for 4 - 6 cycles. | Drug | SMART TNT Plan I |
| CapecitabineAlso: XelodaCapecitabine will be administered orally at a dose of 825 mg/m2 via tablet twice per day (BID) on Day 1, 5 days per week. | Drug | SMART TNT Plan I |
| Accelerated Radiation TherapyAlso: ARTMRI-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 | Radiation | SMART TNT Plan II |
| IrinotecanIrinotecan 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. | Drug | SMART TNT Plan I |
Primary outcome
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.
8 secondary outcomes
Incidence of Acute and Long-Term Toxicity After Start of Study Therapy
Time frame: Up to 30 months
Percentage of Participants with Documented Local Control
Time frame: Up to 2 years
Percentage of Participants with Documented Distant Metastasis
Time frame: Up to 2 years
Disease-free Survival (DFS) rate
Time frame: Up to 2 years
Overall Survival (OS)
Time frame: Up to 2 years
Percentage of Real Negatives
Time frame: Up to 6 months
Health-related Quality of Life (HRQOL) Scores: Patient-Reported Outcomes Measurement Information System (PROMIS)
Time frame: Up to 30 months
Health-related Quality of Life (HRQOL) Scores: Pittsburgh Sleep Quality Index (PSQI)
Time frame: Up to 30 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Benjamin Spieler, MD principal investigator
University of Miami
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Intensity-modulated radiation therapy, 5-fluorouracil and Leucovorin in people with Locally Advanced Rectal Cancer, run by University of Miami at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zuzel Rodriguez (305-243-0124, z.rodriguez1@med.miami.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Toxicity Among Participants After Start Receiving MRI-g Pelvic ART (time frame: Up to 30 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2026.