IXO (Irinotecan, Xeloda, Oxaliplatin) in Rectal Cancer

Study Overview
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Brief Summary
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This is a prospective open label single-arm, single-institution phase II clinical trial to test the efficacy of neoadjuvant treatment with IXO (Irinotecan, Capecitabine [Xeloda], Oxaliplatin) followed by chemoradiotherapy and resection in patients with resectable non-metastatic primary rectal cancer of stage cT3-T4 N0-N2.

Official Title
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A Phase II Trial of Neoadjuvant IXO Regimen (Irinotecan, Capecitabine [Xeloda], Oxaliplatin) Followed by Combined Modality Capecitabine and Radiation for Locally Resectable Advanced Rectal Cancer

Conditions
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Rectal Cancer

Intervention / Treatment
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* Drug: IXO regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: General Pathologically confirmed rectal adenocarcinoma T3 or T4 or N1 (node ≥1 cm on short axis) adenocarcinoma of the rectum. ECOG performance status equal or less than 1 Male and female patients, aged ≥ 18 years and ≤ 80 years Written informed consent Adequate haematological, liver, renal function Resectability Patients categorized as having resectable locally advanced cancer Favorable general condition Exclusion Criteria: Resectability Diagnosis of metastatic disease Clear indication of involvement of pelvic wall(s), on imaging. Peritoneal carcinomatosis, portal vein occlusion, ascites, non-regional lymph nodes Histology other than adenocarcinoma Obstructed rectal carcinoma without defunctionalizing colostomy Prior treatment Previously undergone treatment for this disease Prior chemotherapy for colorectal cancer Prior chemotherapy for other malignancies in past 12 months Prior radiotherapy other than skin cancer Concomitant use of St John's Wort Treatment with any other investigational agent Current use of full-dose of warfarin for therapeutic Other conditions Confirmed or suspected brain metastases History or evidence of CNS disease Past or current history of other malignancies Clinically significant cardiovascular disease Evidence of bleeding diathesis or coagulopathy Known hypersensitivity to any of the study drugs Serious, non-healing wound, ulcer or bone fracture Major surgical procedure or significant traumatic injury within 28 days prior to treatment Disease or condition that contraindicates the use of an investigational drug Life expectancy less than 5 years Inability or unwillingness to comply with the protocol Neuropathy ≥ Gr.2 History of ulcerative colitis or Crohn's disease Pelvic abscess or perforated pelvic carcinoma Pregnancy / Contraception Pregnancy or lactation Positive serum pregnancy test within 7 days of starting study treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IXO regimen<br>single-group | Drug: IXO regimen<br>* IXO regimen is administered as following: irinotecan 160 mg/m2 i.v. (over 60-90 minutes) with oxaliplatin 100 mg/m2 i.v. (over 120 minutes) on day 1, followed by capecitabine 950 mg/m2 PO, b.i.d. on days 2-15, every 3 weeks. Each cycle of IXO lasts 21 days, with the subsequent cycle to start on day 22.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete response (pCR) | To test the efficacy of neoadjuvant treatment with IXO followed by chemoradiotherapy and surgical resection, evaluated as histological therapy-induced tumour regression, assessed by the rate of pathological complete response (pCR) at the primary tumor site (pT0) | 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response | Objective Response by MRI - post IXO and post RCT | 12 weeks and 18 weeks | 
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | Toxicity according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and drug safety | every 3 weeks during neoadjuvant chemotherapy; before CRT; 3rd week of CRT; 2 days, 3 weeks and 6 weeks post CRT; pre-op; 2 days and 4 weeks post-op | 
| Recurrence | Rates of local and distant disease recurrence | q6 months | 
| RFS, PFS, TTR | Recurrence free survival (RFS), progression free survival (PFS), time to recurrence (TTR) | q6 months | 
| Quality of life | Quality of life (QoL) as assessed by the EORTC QLQ-C30 scale | enrolment, 12 weeks, 18 weeks, 26 weeks | 
| Surgical morbidity and mortality | post-operative | 26 weeks | 
| Rate of post-operative sphincter preservation | post-operative | 26 weeks | 
| OS | overall survival (OS) | q6 months first 2 years and annually thereafter | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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locally resectable advanced adenocarcinoma of the rectum