Back to resultsSMART TNT for the Conservative Management of Locally Advanced Rectal Cancer (SMART TNT)
Primary Purpose
Locally Advanced Rectal Cancer
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Intensity-modulated radiation therapy
5-fluorouracil
Leucovorin
Oxaliplatin
Capecitabine
Accelerated Radiation Therapy
Sponsored by
About this trial
This is an interventional treatment trial for Locally Advanced Rectal Cancer
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 lesion found on colonoscopy.
- Previous history of pelvic radiotherapy.
- History of concurrent, active malignancy, other than non metastatic skin cancer within the last 5 years.
- Symptomatic congestive heart failure of New York Heart Association Class III or IV, unstable angina pectoris or serious uncontrolled 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).
- Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition or known HIV seropositivity; note, however, HIV testing is not required for entry into this protocol. The need to exclude patients with HIV/AIDS from this protocol is based on the fact that the treatments involved in this protocol may be significantly immunosuppressive.
- 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).
Sites / Locations
- University of MiamiRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
SMART TNT Plan I
SMART TNT Plan II
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Percentage of Participants with Documented Local Control
Local control is defined as the stopping of cancer growth at the original primary site. The percentage of participants with documented local control after study therapy will be reported.
Percentage of Participants with Documented Distant Metastasis
Distant metastasis is defined as cancer that has spread form the original (primary) tumor to distant organs and distant lymph nodes. The percentage of participants with documented distant metastasis after study therapy will be reported.
Disease-free Survival (DFS) rate
Disease-free survival is defined as the elapsed time after treatment that a person with disease lives without known disease recurrence. DFS rate will be reported as the percentage of participants without disease recurrence after start of treatment.
Overall Survival (OS)
OS will be reported as the number of participants still alive after start of treatment.
Percentage of Real Negatives
The sensitivity and specificity of multiparametric magnetic resonance imaging (mpMRI) to measure tumor response will be reported as the percentage of real negatives during the course of treatment of study participants.
Health-related Quality of Life (HRQOL) Scores: Patient-Reported Outcomes Measurement Information System (PROMIS)
Patient-Reported Outcomes (PRO) will be measured using the 29-item NIH PROMIS questionnaire, a validated HRQOL measure that provides global levels of health-related quality of life. PROMIS has subscales of emotional distress, fatigue, pain, physical function, sleep disturbance, and satisfaction with social participation.
Health-related Quality of Life (HRQOL) Scores: Pittsburgh Sleep Quality Index (PSQI)
Health-related quality of life will be reported using Pittsburgh Sleep Quality Index (PSQI) which assesses patient-reported sleep quality over a 1-month time interval. The PSQI consists of 19 items including 7 sleep components (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction) that produce one global score. Each item is weighted on a 0-3 interval scale. The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05412082
Brief Title
SMART TNT for the Conservative Management of Locally Advanced Rectal Cancer
Acronym
SMART TNT
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 5, 2022 (Actual)
Primary Completion Date
October 2025 (Anticipated)
Study Completion Date
October 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Miami
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Rectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
SMART TNT Plan I
Arm Type
Experimental
Arm Description
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.
Arm Title
SMART TNT Plan II
Arm Type
Experimental
Arm Description
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.
Intervention Type
Radiation
Intervention Name(s)
Intensity-modulated radiation therapy
Other Intervention Name(s)
IMRT
Intervention Description
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
Drug
Intervention Name(s)
5-fluorouracil
Other Intervention Name(s)
5-FU
Intervention Description
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
Intervention Name(s)
Leucovorin
Other Intervention Name(s)
Folinic acid
Intervention Description
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
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
Eloxatin
Intervention Description
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
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Intervention Description
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
Radiation
Intervention Name(s)
Accelerated Radiation Therapy
Other Intervention Name(s)
ART
Intervention Description
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
Primary Outcome Measure Information:
Title
Incidence of Toxicity Among Participants After Start Receiving MRI-g Pelvic ART
Description
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.
Time Frame
Up to 30 months
Secondary Outcome Measure Information:
Title
Incidence of Acute and Long-Term Toxicity After Start of Study Therapy
Description
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.
Time Frame
Up to 30 months
Title
Percentage of Participants with Documented Local Control
Description
Local control is defined as the stopping of cancer growth at the original primary site. The percentage of participants with documented local control after study therapy will be reported.
Time Frame
Up to 2 years
Title
Percentage of Participants with Documented Distant Metastasis
Description
Distant metastasis is defined as cancer that has spread form the original (primary) tumor to distant organs and distant lymph nodes. The percentage of participants with documented distant metastasis after study therapy will be reported.
Time Frame
Up to 2 years
Title
Disease-free Survival (DFS) rate
Description
Disease-free survival is defined as the elapsed time after treatment that a person with disease lives without known disease recurrence. DFS rate will be reported as the percentage of participants without disease recurrence after start of treatment.
Time Frame
Up to 2 years
Title
Overall Survival (OS)
Description
OS will be reported as the number of participants still alive after start of treatment.
Time Frame
Up to 2 years
Title
Percentage of Real Negatives
Description
The sensitivity and specificity of multiparametric magnetic resonance imaging (mpMRI) to measure tumor response will be reported as the percentage of real negatives during the course of treatment of study participants.
Time Frame
Up to 6 months
Title
Health-related Quality of Life (HRQOL) Scores: Patient-Reported Outcomes Measurement Information System (PROMIS)
Description
Patient-Reported Outcomes (PRO) will be measured using the 29-item NIH PROMIS questionnaire, a validated HRQOL measure that provides global levels of health-related quality of life. PROMIS has subscales of emotional distress, fatigue, pain, physical function, sleep disturbance, and satisfaction with social participation.
Time Frame
Up to 30 months
Title
Health-related Quality of Life (HRQOL) Scores: Pittsburgh Sleep Quality Index (PSQI)
Description
Health-related quality of life will be reported using Pittsburgh Sleep Quality Index (PSQI) which assesses patient-reported sleep quality over a 1-month time interval. The PSQI consists of 19 items including 7 sleep components (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction) that produce one global score. Each item is weighted on a 0-3 interval scale. The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality.
Time Frame
Up to 30 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 lesion found on colonoscopy.
Previous history of pelvic radiotherapy.
History of concurrent, active malignancy, other than non metastatic skin cancer within the last 5 years.
Symptomatic congestive heart failure of New York Heart Association Class III or IV, unstable angina pectoris or serious uncontrolled 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).
Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition or known HIV seropositivity; note, however, HIV testing is not required for entry into this protocol. The need to exclude patients with HIV/AIDS from this protocol is based on the fact that the treatments involved in this protocol may be significantly immunosuppressive.
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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zuzel Rodriguez
Phone
305-243-0124
Email
z.rodriguez1@med.miami.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lorraine Portelance, MD
Organizational Affiliation
University of Miami
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zuzel Rodriguez
Phone
305-243-0124
Email
z.rodriguez1@med.miami.edu
First Name & Middle Initial & Last Name & Degree
Lorraine Portelance, MD
Phone
305-243-4200
Email
lportelance@med.miami.edu
First Name & Middle Initial & Last Name & Degree
Lorraine Portelance, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
SMART TNT for the Conservative Management of Locally Advanced Rectal Cancer
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