clinical study to evaluate the efficacy of a two drug combination versus a single drug therapy in the treatment of locally advanced rectal cancer.

Phase 1

• Conditions: locally advanced rectal cancer; MedDRA version: 17.0Level: PTClassification code 10038050Term: Rectal cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 17.0Level: PTClassification code 10038049Term: Rectal cancer stage IISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2006-006532-21-DE
• Lead Sponsor: EORTC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2008-11-17
• Study Completion: 2015-12-31
• Last Update Posted: 10 January 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1094

Inclusion Criteria

Male or female patients with histologically proven adenocarcinoma of the rectum (tumour = 12
cm from the anal verge as assessed by rigid proctoscopy).
¨ Clinical tumour stage T3/4 or any node-positive disease (clinical stage according the TNM
classification system (Appendix J), positive nodes as diagnosed on endorectal ultrasound and/or
MRI). Tumour is staged by preferably a high resolution MRI. If MRI is not available,
locoregional staging must be performed by computed tomography plus endorectal ultrasound.
¨ No evidence of metastatic disease (as evidenced by negative CT-scan of the chest and
abdomen).
¨ The disease must be considered either resectable at the time of entry or expected to become
resectable after preoperative chemoradiation.
¨ Age = 18 years.
¨ WHO/ECOG Performance Status = 2
¨ No prior cytotoxic chemotherapy or radiotherapy for rectal cancer.
¨ No prior radiotherapy to the pelvis, for any reason.
¨ Presence of adequate contraception in fertile patients. Adequate methods of contraception are:
intra-uterine device, hormonal contraception, condom use with spermicide. Pregnant or
breastfeeding women are excluded from participation.
¨ Adequate bone marrow, hepatic and renal function:
¨ Haemoglobin = 10.0 g/dL (transfusions allowed to achieve or maintain levels), absolute
neutrophil count = 1.5 x 109/L, platelet count = 100 x 109/L,
¨ ALAT, ASAT = 2.5 x ULN,
¨ Alkaline phosphatase = 2.5 x ULN,
¨ Total bilirubin = 1.5 x ULN,
¨ Creatinine clearance > 50 mL/min (calculated according to Cockroft and Gault) and
¨ Creatinine = 1.5 x ULN.
¨ Ability to swallow tablets.
¨ Patient must not have been treated with any investigational drug, agent nor procedure, (i.e. did
not participate in another trial within 4 weeks) before entry in this trial.
No previous (within the last 5 years) or concurrent malignancies, with the exception of
adequately treated cone-biopsied in situ carcinoma of the cervix or basal cell carcinoma of the
skin.
¨ No clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic
coronary artery disease and cardiac arrhythmia not well controlled with medication) or
myocardial infarction within the last 12 months.
¨ No known allergy or any other adverse reaction to any of the study drugs or to any related
compound.
¨ No known dihydropyrimidine dehydrogenase deficiency.
¨ No known significant impairment of intestinal resorption (e.g. chronic diarrhoea, inflammatory
bowel disease).
¨ No pre-existing condition which would deter chemoradiotherapy or radiotherapy, i.e. fistulas,
severe ulcerative colitis (particularly patients currently taking sulphasalazine), Crohn’s disease,
prior adhesions.
¨ No peripheral neuropathy = grade 2 (according to CTCAE v3.0)
¨ No serious uncontrolled intercurrent infections or other serious uncontrolled concomitant
disease.
¨ No organ allograft requiring immunosuppressive therapy.
¨ No requirement for concurrent use of the antiviral agent sorivudine or chemically related
analogues, such as brivudine.
¨ No history of uncontrolled seizures, central nervous system disorders or psychiatric disability
judged by the investigator to be clinically significant precluding informed consent or interfering
with compliance for oral drug intake.
¨ No psychological, familial, sociological or geographical condition potentially hampering
compliance with the study protocol and follow-up schedule (these conditions should be
discussed with the patient before registration in the tr

Exclusion Criteria

-severe renal impairment (creatinine clearance below 30 ml/min)
-pregnancy and lactation
-hypersensitivity to capecitabine or 5-FU or to any of the excipients
-patients with history of severe and unexpected reactions to fluoro pyrimidine therapy
-patients with known dihydropyrimidine dehydrogenase (DPD) deficiency
-patients with severe leucopenia, neutropenia and thrombocytopenia
-severe hepatic impairment
-concomittant use of sorivudine or its chemically related analogues such as brivudine
-patients with known allergy against oxaliplatin or other platinum compounds
-patients with impaired bone marrow function
-patients with pre-excisting peripheral neuropathy

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate whether the addition of oxaliplatin to preoperative fluoropyrimidine-based chemoradiation and postoperative fluoropyrimidine-based chemotherapy improves disease-free survival in patients with locally advanced rectal cancer. Disease-free survival is defined as the interval from randomization to loco-regional failure, metastatic recurrence, the appearance of a secondary colorectal cancer or death, whichever occurs first.<br>;Secondary Objective: secondary objectives are to compare the two treatment arms with respect to overall survival, loco-regional failure, distant failure, pathological down-staging (ypT0-2N0) rate, pathological complete remission (ypT0N0) rate, tumor regression grade, histopathological R0 resection rate, sphincter preservation rate, perioperative complication rate, toxicity (CTC).<br><br>;Primary end point(s): The primary endpoint is disease-free survival;Timepoint(s) of evaluation of this end point: february 2016

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Secondary objectives are to compare the two treatment arms with<br>respect to overall survival, loco-regional failure, distant failure,<br>pathological down-staging (ypT0-2N0) rate, pathological complete<br>remission (ypT0N0) rate, tumor regression grade, histopathological R0<br>resection rate, sphincter preservation rate, perioperative complication<br>rate, toxicity (CTC).<br>¨ Ancillary studies will be conducted with the aim of predicting the risk<br>of peri-operative complications in elderly patients by means of the Preoperative<br>Assessment of Cancer in the Elderly (PACE) instruments. In<br>addition, material will be collected for future translational research (see<br>below).;Timepoint(s) of evaluation of this end point: N.A.