SMART TNT for the Conservative Management of Locally Adva... | NCT05412082

NCT05412082

Protocol Section

Identification Module

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
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.	Up to 30 months

Eligibility Module

Eligibility Criteria

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.
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).

ID	Term
D050397	Radiotherapy, Intensity-Modulated
D005472	Fluorouracil
D002955	Leucovorin
D000077150	Oxaliplatin
D000069287	Capecitabine
D000077146	Irinotecan

ID	Term
D020266	Radiotherapy, Conformal
D011881	Radiotherapy, Computer-Assisted
D011878	Radiotherapy
D013812	Therapeutics