IXO (Irinotecan, Xeloda, Oxaliplatin) in Rectal Cancer (IXOr)

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

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.

Study Overview

• Status: Unknown
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: IXO regimen

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IXO regimen; single-group	Drug: IXO regimen; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Collaborators: Sanofi; Hoffmann-La Roche; Ottawa Regional Cancer Foundation
• Investigators: Principal Investigator: Derek Jonker, MD, The Ottawa Hospital Cancer Centre

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Anticipated): December 1, 2012
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: August 25, 2010
• First Submitted That Met QC Criteria: November 8, 2010
• First Posted (Estimate): November 9, 2010

Study Record Updates

• Last Update Posted (Estimate): October 15, 2012
• Last Update Submitted That Met QC Criteria: October 12, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: locally resectable advanced adenocarcinoma of the rectum
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: OTT 09-02