Locally Advanced Rectal Cancer
Conditions
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.
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.
Sponsors
University of Miami
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Toxicity Among Participants After Start Receiving MRI-g Pelvic ART | Up to 30 months | 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
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Acute and Long-Term Toxicity After Start of Study Therapy | Up to 30 months | 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 | Up to 2 years | 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 | Up to 2 years | 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 | Up to 2 years | 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) | Up to 2 years | OS will be reported as the number of participants still alive after start of treatment. |
| Percentage of Real Negatives | Up to 6 months | 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) | Up to 30 months | 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) | Up to 30 months | 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. |
Countries
United States
Contacts
CONTACTZuzel Rodriguez
PRINCIPAL_INVESTIGATORBenjamin Spieler, MD
University of Miami
Outcome results
None listed