IXOr: IXO (Irinotecan, Xeloda, Oxaliplatin) in Rectal Cancer
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- Pathological complete response (pCR) [26 weeks]
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 [12 weeks and 18 weeks]
Objective Response by MRI - post IXO and post RCT
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability [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]
Toxicity according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and drug safety
- Recurrence [q6 months]
Rates of local and distant disease recurrence
- RFS, PFS, TTR [q6 months]
Recurrence free survival (RFS), progression free survival (PFS), time to recurrence (TTR)
- Quality of life [enrolment, 12 weeks, 18 weeks, 26 weeks]
Quality of life (QoL) as assessed by the EORTC QLQ-C30 scale
- Surgical morbidity and mortality [26 weeks]
post-operative
- Rate of post-operative sphincter preservation [26 weeks]
post-operative
- OS [q6 months first 2 years and annually thereafter]
overall survival (OS)
Eligibility Criteria
Criteria
Inclusion Criteria:
General
-
Pathologically confirmed rectal adenocarcinoma
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T3 or T4 or N1 (node ≥1 cm on short axis) adenocarcinoma of the rectum.
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ECOG performance status equal or less than 1
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Male and female patients, aged ≥ 18 years and ≤ 80 years
-
Written informed consent
-
Adequate haematological, liver, renal function
Resectability
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Patients categorized as having resectable locally advanced cancer
-
Favorable general condition
Exclusion Criteria:
Resectability
-
Diagnosis of metastatic disease
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Clear indication of involvement of pelvic wall(s), on imaging.
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Peritoneal carcinomatosis, portal vein occlusion, ascites, non-regional lymph nodes
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Histology other than adenocarcinoma
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Obstructed rectal carcinoma without defunctionalizing colostomy
Prior treatment
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Previously undergone treatment for this disease
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Prior chemotherapy for colorectal cancer
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Prior chemotherapy for other malignancies in past 12 months
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Prior radiotherapy other than skin cancer
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Concomitant use of St John's Wort
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Treatment with any other investigational agent
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Current use of full-dose of warfarin for therapeutic
Other conditions
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Confirmed or suspected brain metastases
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History or evidence of CNS disease
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Past or current history of other malignancies
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Clinically significant cardiovascular disease
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Evidence of bleeding diathesis or coagulopathy
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Known hypersensitivity to any of the study drugs
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Serious, non-healing wound, ulcer or bone fracture
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Major surgical procedure or significant traumatic injury within 28 days prior to treatment
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Disease or condition that contraindicates the use of an investigational drug
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Life expectancy less than 5 years
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Inability or unwillingness to comply with the protocol
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Neuropathy ≥ Gr.2
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History of ulcerative colitis or Crohn's disease
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Pelvic abscess or perforated pelvic carcinoma
Pregnancy / Contraception
-
Pregnancy or lactation
-
Positive serum pregnancy test within 7 days of starting study treatment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Ottawa Hospital Cancer Centre | Ottawa | Ontario | Canada | K1H 8L6 |
Sponsors and Collaborators
- Ottawa Hospital Research Institute
- Ottawa Regional Cancer Foundation
- Sanofi
- Hoffmann-La Roche
Investigators
- Principal Investigator: Derek Jonker, MD, The Ottawa Hospital Cancer Centre
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- OTT 09-02