SMART TNT for the Conservative Management of Locally Advanced Rectal Cancer

NCT05412082 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: 20210172
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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 surgery.

Conditions

Locally Advanced Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 30 months

Secondary Outcomes (8)

• Incidence of Acute and Long-Term Toxicity After Start of Study Therapy

  Up to 30 months

• Percentage of Participants with Documented Local Control

  Up to 2 years

• Percentage of Participants with Documented Distant Metastasis

  Up to 2 years

• Disease-free Survival (DFS) rate

  Up to 2 years

• Overall Survival (OS)

  Up to 2 years

Study Arms (2)

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.

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.

Radiation: Accelerated Radiation Therapy

Interventions

Intensity-modulated radiation therapy RADIATION

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.

Also known as: IMRT

SMART TNT Plan I

Leucovorin DRUG

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.

Also known as: Folinic acid

SMART TNT Plan I

Oxaliplatin DRUG

Oxaliplatin dose of 85 mg/m2 will be administered intravenously (IV) on Day 1 of each 14-day cycle for 4 - 6 cycles.

Also known as: Eloxatin

SMART TNT Plan I

Capecitabine DRUG

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.

Also known as: Xeloda

SMART TNT Plan I

Accelerated Radiation Therapy RADIATION

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

Also known as: ART

SMART TNT Plan II

Irinotecan DRUG

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.

SMART TNT Plan I

5-fluorouracil DRUG

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.

Also known as: 5-FU

SMART TNT Plan I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Miami: lead

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

RECRUITING

MeSH Terms

Interventions

Radiotherapy, Intensity-Modulated; Fluorouracil; Leucovorin; Oxaliplatin; Capecitabine; Irinotecan

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Camptothecin; Alkaloids

Study Officials

• Benjamin Spieler, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zuzel Rodriguez

CONTACT

305-243-0124; z.rodriguez1@med.miami.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Clinical

Study Record Dates

• First Submitted: June 6, 2022
• First Posted: June 9, 2022
• Study Start: October 5, 2022
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2028
• Last Updated: February 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)