Health Condition 1: C20- Malignant neoplasm of rectum
Conditions
Interventions
Intervention1: mFOLFIRINOX And Long Course Chemoradiation as Total Neoadjuvant Therapy: The patients will receive neoadjuvant chemotherapy with mFOLFIRINOX for 4 cycles followed by Long course chemora
Sponsors
Tata Memorial Hospital
Eligibility
Inclusion criteria
Inclusion criteria: Adults of either sex aged more than 18 years who are willing to provide written informed consent. Histologically confirmed rectal adenocarcinoma located within less than 15 centimeters from the anal verge. Eastern Cooperative Oncology Group performance status of 0, 1, or 2. Presence of at least one high-risk feature, including cT3 disease with mesorectal fascia involvement, cT4 disease, extramural vascular invasion, signet ring cell carcinoma or poorly differentiated adenocarcinoma in node-positive or T3 and above disease, or presence of lateral pelvic lymph nodes on pelvic magnetic resonance imaging. Tumors considered resectable or potentially resectable after chemoradiation and patients who are medically fit for surgery. Use of adequate contraception in patients of reproductive potential, with a negative pregnancy test required for women of childbearing potential. Adequate hematological, liver, and renal function at the time of study inclusion.
Exclusion criteria
Exclusion criteria: Patients meeting any of the following criteria will be excluded from the study: Patients with distant metastases, including para aortic lymph nodes. Para aortic node negativity must be confirmed by radiological or histological assessment before study consideration. Patients suitable for a PROSPECT type neoadjuvant approach, including upper or mid rectal T3 tumors without mesorectal fascia involvement, limited nodal disease, no lateral pelvic nodes, and no extramural vascular invasion. Patients with signet ring rectal adenocarcinoma staged as T3 N0 without extramural vascular invasion or lateral pelvic lymph nodes. Patients with low rectal adenocarcinoma who are candidates for intersphincteric resection or non operative management such as a wait and watch approach, as determined by the multidisciplinary team prior to screening. Patients with microsatellite instability high tumors. Patients with rectal cancer histology other than adenocarcinoma. Patients with a history of coronary artery disease, including angina or myocardial infarction. Patients with known homozygous dihydropyrimidine dehydrogenase deficiency. Patients with grade two or higher sensory or motor neuropathy. Patients with known hypersensitivity or contraindications to any study related medication. Patients with another active malignancy or a past history of malignancy, except for treated carcinoma in situ of the cervix or basal cell carcinoma of the skin. Patients with human immunodeficiency virus, hepatitis B, or hepatitis C infection requiring active antiviral therapy at screening. Pregnant or breastfeeding women. Patients with active progressive infection or any other serious medical condition that may interfere with study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of the study is to evaluate whether total neoadjuvant therapy using modified FOLFIRINOX chemotherapy followed by long course chemoradiation improves outcomes compared with short course radiotherapy followed by modified FOLFOX or CAPOX chemotherapy, as measured by three year event free survival.Timepoint: Primary Objective will be measured by event-free survival at 3 years from the time of randomization. | — |
Secondary
| Measure | Time frame |
|---|---|
| Pathological Complete Response (pCR) ratesTimepoint: pCR rate is defined as the percentage of patients, relative to the total of enrolled subjects, achieving complete histological regression with no available tumor cells ypT0N0. This will be measured by the MANDARD criteria. In brief, the Mandard scoring is as follows TRG1â??No residual tumor, presence of fibrosis; TRG2â??Rare residual tumor cells scattered through fibrosis; TRG3â??Increased residual tumor cells but fibrosis is predominant; TRG4â??Residual tumor cells outgrowing fibrosis; TRG5â??Absence of regression Patients with a TRG1 score will be considered to have achieved a pCR. ;R0 resection ratesTimepoint: R0 resection rate is defined as the percentage of patients, relative to the total of enrolled subjects, undergoing R0 resection of the primary tumor after the commencement of neoadjuvant therapy.;Local Recurrence-free Survival at 3 yearsTimepoint: from randomization to local or locoregional progression (either at primary or nodal sites), without appearance of concurrent distant metastases. Patients who have concurrent distant metastases will be classified otherwise;Overall Survival at 3 yearsTimepoint: OS is defined as the time from randomization to the time of occurrence of death;To compare toxicities for both the armsTimepoint: according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, postoperative complication rate, and late toxicity rate at 1 year after surgery. | — |
Countries
India
Contacts
Public ContactDr Anant Ramaswamy
Tata Memorial Hospital
Outcome results
None listed