Colon Neoadjuvant FOLFOXIRI Study

Study Overview
=================
Brief Summary
-----------------
Objective tumour response rate to FOLFOXIRI to pre-operative therapy.

Official Title
-----------------
A Phase II Study of Neoadjuvant FOLFOXIRI Followed by Concurrent Capecitabine and Radiotherapy for High Risk Rectal Cancer

Conditions
-----------------
Rectal Cancer

Intervention / Treatment
-----------------
* Drug: neoadjuvant FOLFOXIRI
* Drug: Capecitabine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age >= 18 years of either sex. ECOG performance status 0-1 Measurable disease by RECIST 1.1 criteria. Histologically confirmed rectal adenocarcinoma (defined as either mid- or low rectal cancer that is located within 12 cm from the anal verge OR below the peritoneal reflection) that is previously untreated. 'High risk' rectal cancer, or rectal cancers that are considered marginally operable where there is a significant risk of positive surgical margin: T3 (low-lying tumour at or below the levators) or T4, or Tumour infiltrating perirectal fat, or Any T-stage (T1-4) and node-positive tumour (invading surrounding structures or peritoneum) Adequate bone marrow, renal and hepatic function as defined by: absolute neutrophil count >= 1.5 x 109/L, hemoglobin >= 9 g/L, platelets >= 100 x 109/L, calculated creatinine clearance >= 55 ml/min, total bilirubin =<1.5 x the upper limit of normal, alanine aminotransferase (ALT) =<2.5 upper limit of normal. Exclusion Criteria: Known distant metastasis, even if the metastasis has been resected. History of another invasive malignancy within the last 5 years, except for treated basal cell carcinoma of the skin, cervical intraepithelial neoplasia, or non-invasive DCIS of the breast. Upper rectal cancer that is located above the peritoneal reflection. Primary tumour associated with any one of the following features: Frank intestinal obstruction, or Endoscope unable to pass through the tumour's lumen plus worsening local obstructive symptoms. Note: Patients with such features should be assessed by the surgical team regarding stomal bypass prior to study enrolment. Such patients can still be considered for study enrolment after undergoing stomal bypass. Known hypersensitivity reaction to the study drugs (i.e. fluoropyrimidine, irinotecan, oxaliplatin) Known peripheral neuropathy of grade 2 or more in severity. Patients who have received an experimental anticancer therapy within the last 28 days. Previous pelvic radiotherapy. Previous oxaliplatin or irinotecan for the treatment of colon or rectal cancer Patient with hip prosthesis Major surgery within the last 28 days. Exception: Any patient who underwent stomal bypass for obstructing primary tumour within the last 14 days are still eligible, as long as the patient has sufficiently recovered from the surgery at the investigator's discretion.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: neoadjuvant FOLFOXIRI<br> | Drug: neoadjuvant FOLFOXIRI<br> <br> Drug: Capecitabine<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective tumour response rate |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumour regression grade |  | 2 years | 
| pathologic complete response |  | 2 years | 
| Rate of circumferential resection margin (CRM) clearance |  | 2 years | 
| Rate of tumour downstaging |  | 2 years | 
| Number of Participants with Adverse Events |  | 2 years | 
| Overall survival |  | 5 years | 
| disease-free survival, relapse-free survival |  | 5 years | 
| Time to local (and distant) recurrence |  | 5 years | 
| Number of patients with 30-day post-operative mortality |  | 1 month | 
| Compliance to study treatment |  | 2 years | 
| Number of response to neoadjuvant therapy |  | 2 years |