IXO (Irinotecan, Xeloda, Oxaliplatin) in Rectal Cancer (IXOr)
Primary Purpose
Rectal Cancer
Status
Unknown status
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
IXO regimen
Sponsored by
About this trial
This is an interventional treatment trial for Rectal Cancer focused on measuring locally resectable advanced adenocarcinoma of the rectum
Eligibility Criteria
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
Sites / Locations
- The Ottawa Hospital Cancer Centre
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
IXO regimen
Arm Description
single-group
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
Objective Response
Objective Response by MRI - post IXO and post RCT
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
Recurrence
Rates of local and distant disease recurrence
RFS, PFS, TTR
Recurrence free survival (RFS), progression free survival (PFS), time to recurrence (TTR)
Quality of life
Quality of life (QoL) as assessed by the EORTC QLQ-C30 scale
Surgical morbidity and mortality
post-operative
Rate of post-operative sphincter preservation
post-operative
OS
overall survival (OS)
Full Information
NCT ID
NCT01237665
First Posted
August 25, 2010
Last Updated
October 12, 2012
Sponsor
Ottawa Hospital Research Institute
Collaborators
Ottawa Regional Cancer Foundation, Sanofi, Hoffmann-La Roche
1. Study Identification
Unique Protocol Identification Number
NCT01237665
Brief Title
IXO (Irinotecan, Xeloda, Oxaliplatin) in Rectal Cancer
Acronym
IXOr
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2012
Overall Recruitment Status
Unknown status
Study Start Date
September 2010 (undefined)
Primary Completion Date
December 2012 (Anticipated)
Study Completion Date
December 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ottawa Hospital Research Institute
Collaborators
Ottawa Regional Cancer Foundation, Sanofi, Hoffmann-La Roche
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Cancer
Keywords
locally resectable advanced adenocarcinoma of the rectum
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
IXO regimen
Arm Type
Experimental
Arm Description
single-group
Intervention Type
Drug
Intervention Name(s)
IXO regimen
Intervention Description
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.
Primary Outcome Measure Information:
Title
Pathological complete response (pCR)
Description
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)
Time Frame
26 weeks
Secondary Outcome Measure Information:
Title
Objective Response
Description
Objective Response by MRI - post IXO and post RCT
Time Frame
12 weeks and 18 weeks
Title
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Description
Toxicity according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and drug safety
Time Frame
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
Title
Recurrence
Description
Rates of local and distant disease recurrence
Time Frame
q6 months
Title
RFS, PFS, TTR
Description
Recurrence free survival (RFS), progression free survival (PFS), time to recurrence (TTR)
Time Frame
q6 months
Title
Quality of life
Description
Quality of life (QoL) as assessed by the EORTC QLQ-C30 scale
Time Frame
enrolment, 12 weeks, 18 weeks, 26 weeks
Title
Surgical morbidity and mortality
Description
post-operative
Time Frame
26 weeks
Title
Rate of post-operative sphincter preservation
Description
post-operative
Time Frame
26 weeks
Title
OS
Description
overall survival (OS)
Time Frame
q6 months first 2 years and annually thereafter
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Derek Jonker, MD
Organizational Affiliation
The Ottawa Hospital Cancer Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Ottawa Hospital Cancer Centre
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
IXO (Irinotecan, Xeloda, Oxaliplatin) in Rectal Cancer
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