Rectal Cancer
Conditions
Keywords
locally resectable advanced adenocarcinoma of the rectum
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.
Interventions
DRUGIXO 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.
Sponsors
Ottawa Regional Cancer Foundation
Sanofi
Hoffmann-La Roche
Ottawa Hospital Research Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| Objective Response | 12 weeks and 18 weeks | Objective Response by MRI - post IXO and post RCT |
| 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) |
| Quality of life | enrolment, 12 weeks, 18 weeks, 26 weeks | Quality of life (QoL) as assessed by the EORTC QLQ-C30 scale |
Countries
Canada
Outcome results
None listed