SMART TNT for the Conservative Management of Locally Advanced Rectal Cancer

NCT ID: NCT05412082

Last Updated: 2025-03-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-05

Study Completion Date

2027-10-31

Brief Summary

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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.

Detailed Description

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Conditions

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Locally Advanced Rectal Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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SMART TNT Plan I

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.

Group Type EXPERIMENTAL

Intensity-modulated radiation therapy

Intervention Type 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.

5-fluorouracil

Intervention Type 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.

Leucovorin

Intervention Type 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.

Oxaliplatin

Intervention Type DRUG

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

Capecitabine

Intervention Type 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.

Irinotecan

Intervention Type 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 II

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.

Group Type EXPERIMENTAL

Accelerated Radiation Therapy

Intervention Type 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

Interventions

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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.

Intervention Type RADIATION

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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

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

Intervention Type RADIATION

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.

Intervention Type DRUG

Other Intervention Names

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IMRT 5-FU Folinic acid Eloxatin Xeloda ART

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Miami

OTHER

Sponsor Role lead

Responsible Party

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Benjamin Spieler

Assistant Professor of Clinical

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Benjamin Spieler, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

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University of Miami

Miami, Florida, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Zuzel Rodriguez

Role: CONTACT

305-243-0124

Facility Contacts

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Zuzel Rodriguez

Role: primary

305-243-0124

Benjamin Spieler, MD

Role: backup

305-243-4229

Other Identifiers

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20210172

Identifier Type: -

Identifier Source: org_study_id

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