RecruitingPhase 1NCT05412082

SMART TNT for the Conservative Management of 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


Sponsor

University of Miami

Enrollment

25 participants

Start Date

Oct 5, 2022

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 Years

Inclusion Criteria9

  • 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 Criteria12

  • 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.
  • 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).

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Interventions

RADIATIONIntensity-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.

DRUG5-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.

DRUGLeucovorin

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.

DRUGOxaliplatin

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

DRUGCapecitabine

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.

RADIATIONAccelerated 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

DRUGIrinotecan

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.


Locations(1)

University of Miami

Miami, Florida, United States

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NCT05412082


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