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Anti-metabolites

Chemoradiation for Rectal Cancer (SMART TNT Trial)

Phase 1

Recruiting

Led By Lorraine Portelance, MD

Research Sponsored by University of Miami

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Primary tumor located ≤18 cm from margin verge

Patients with newly diagnosed, biopsy proven, rectal adenocarcinoma

Must not have

Previous history of pelvic radiotherapy

Active (acute or chronic) or uncontrolled severe infections requiring intravenous antibiotics or active tuberculosis (TB)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

All Individual Drugs Already Approved

Approved for 5 Other Conditions

No Placebo-Only Group

Summary

This trial is testing whether it's safe and effective to give chemotherapy to patients with locally advanced rectal cancer before radiation therapy, and whether a higher dose of radiation therapy can help patients avoid surgery.

Who is the study for?

This trial is for adults with newly diagnosed rectal cancer that hasn't spread beyond the pelvis. Participants must have a certain level of physical fitness (ECOG 0-2), acceptable liver function, and no severe heart conditions or immune deficiencies. Pregnant women and those with metal implants incompatible with MRI are excluded.

What is being tested?

The study tests if starting with chemotherapy followed by higher-than-usual doses of radiation can help patients avoid surgery while effectively treating locally advanced rectal cancer. The chemo drugs used include 5-fluorouracil, Leucovorin, Oxaliplatin, and Capecitabine.

What are the potential side effects?

Potential side effects may include skin changes or irritation from radiation, fatigue, nausea, diarrhea from chemotherapy drugs, increased risk of infections due to lowered white blood cell counts, and possible nerve damage leading to numbness or tingling.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My tumor is within 18 cm of the anal verge.

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I have been recently diagnosed with rectal cancer.

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I am 18 years old or older.

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My primary tumor is classified as T3N0 or has positive nodes based on MRI.

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I am able to care for myself and perform daily activities.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had radiation therapy in the pelvic area before.

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I do not have severe infections needing IV antibiotics or active TB.

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I have moderate to severe numbness, tingling, or muscle weakness.

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I have not had any cancer other than non-spreading skin cancer in the last 5 years.

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My initial scans showed cancer has spread to other parts of my body.

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I do not have severe heart failure, recent heart attacks, or uncontrolled heart rhythm problems.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of Toxicity Among Participants After Start Receiving MRI-g Pelvic ART

Secondary study objectives

Disease-free Survival (DFS) rate

Health-related Quality of Life (HRQOL) Scores: Patient-Reported Outcomes Measurement Information System (PROMIS)

Health-related Quality of Life (HRQOL) Scores: Pittsburgh Sleep Quality Index (PSQI)

+5 more

Side effects data

From 2022 Phase 3 trial • 940 Patients • NCT00265941

96%

Dysphagia

79%

Dry mouth

78%

Radiation mucositis

72%

Fatigue

59%

Hemoglobin

59%

Dermatitis radiation NOS

57%

Weight decreased

56%

Nausea

55%

Dysgeusia

54%

Mucositis/stomatitis (clinical exam): Pharynx

49%

Skin fibrosis

47%

Laryngeal edema

46%

Leukopenia NOS

41%

Pharyngolaryngeal pain

40%

Salivary gland disorder NOS

40%

Laryngitis NOS

38%

Vomiting NOS

38%

Constipation

37%

Hyponatremia

36%

Anorexia

34%

Dermatology/skin - Other

33%

Hyperglycemia NOS

32%

Oral pain

30%

Neutrophil count

29%

Radiation recall syndrome

28%

Hypoalbuminemia

28%

Hearing impaired

27%

Edema: head and neck

26%

Tinnitus

26%

Dehydration

25%

Cough

25%

Peripheral sensory neuropathy

24%

Blood creatinine increased

24%

Hypomagnesemia

22%

Lymphopenia

22%

Platelet count decreased

22%

Trismus

21%

Neuralgia NOS

21%

Alopecia

21%

Skin hyperpigmentation

20%

Hypocalcemia

19%

Alanine aminotransferase increased

19%

Hypokalemia

19%

Mucositis/stomatitis (clinical exam): Larynx

18%

Hypothyroidism

18%

Neck pain

17%

Diarrhea NOS

16%

Aspartate aminotransferase increased

15%

Insomnia

14%

Anxiety

14%

Pain - Other

14%

Depression

13%

Dermatitis exfoliative NOS

13%

Pyrexia

13%

Dyspnea

13%

Headache

12%

Dyspepsia

12%

Gastrointestinal - Other

11%

Blood alkaline phosphatase increased

11%

Pulmonary/upper respiratory - Other

10%

Metabolic/laboratory - Other

10%

Osteonecrosis

10%

Dizziness

Tooth disorder NOS

Hyperkalemia

Ear pain

Pruritus

Telangiectasia

Blood/bone marrow - Other

Febrile neutropenia

Musculoskeletal/soft tissue - Other

Hypotension NOS

Aspiration

Hypermagnesemia

Dry skin

Abdominal pain NOS

Esophageal stenosis acquired

Pain NOS

Gingival infection

Back pain

Skin hypopigmentation

Edema: limb

Infection - Other

Fibrosis-deep connective tissue

Muscle weakness NOS

Hiccups

Laryngeal discomfort

Peripheral motor neuropathy

Renal failure NOS

Rigors

Blood bilirubin increased

Esophagitis NOS

Acne NOS

Pneumonia NOS

Confusional state

Hypoxia

Vascular access NOS complication

Myocardial ischemia

Stomatitis

Constitutional Symptoms - Other

Infection with normal ANC or Grade 1 or 2 neutrophils: Blood

Troponin I increased

Mucositis/stomatitis (functional/symptomatic): Larynx

Thrombosis

Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Catheter-related

Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Wound

Depressed level of consciousness

100%

80%

60%

40%

20%

Study treatment Arm

RT + Cisplatin

RT + Cisplatin + Cetuximab

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: SMART TNT Plan IIExperimental Treatment1 Intervention

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 II: SMART TNT Plan IExperimental Treatment5 Interventions

Participants will initiate therapy with neoadjuvant chemotherapy of either six (6) 14-day cycles of 5-fluorouracil + leucovorin + oxaliplatin (FOLFOX) 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Leucovorin

FDA approved

Fluorouracil

FDA approved

Capecitabine

FDA approved

Intensity-modulated radiation therapy

2006