Clinical trial NCT01152710: Capecitabine as Radiosensitising Agent in Neoadjuvant Treatment of Locally Advanced Resectable Rectal Cancer
Official title: Capecitabine as Radiosensitising Agent in Neoadjuvant Treatment of Locally Advanced Resectable Rectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Resectable Rectal Cancer Clinical Stage II and III
Keywords: capecitabine
chemoradiation
rectal cancer
phase II study
Lead sponsor: Institute of Oncology Ljubljana
Sponsor class: OTHER
First posted: 2010-06-29
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A Phase II study aimed to evaluate the efficacy and toxicity of preoperative chemoradiotherapy with capecitabine in locally advanced resectable rectal cancer.

Detailed description: Preoperative chemoradiation has become a standard part of treatment protocols in stage II and III rectal cancer. Compared to postoperative chemoradiotherapy, the advantage of preoperative application of chemotherapeutics and irradiation includes improved compliance, reduced toxicity and downstaging of the tumour in a substantial number of patients. The latter may enhance the rate of curative surgery, permit sphincter preservation in patients with low-sited tumours and have a positive impact on the quality of life of these patients. Orally administered capecitabine (Xeloda®, Hoffmann - La Roche Ltd, Basel, Switzerland) mimics the pharmacokinetics of continuous 5-FU infusion and makes chemoradiotherapy more patient-friendly. The mechanism of capecitabine activation, preferably in tumour cells, may further enhance its efficacy and tolerability, offering the potential for an enhanced therapeutic ratio.The aim of the present phase II study was to evaluate the efficacy and toxicity of preoperative chemoradiotherapy with capecitabine in patients with locally advanced rectal cancer. The primary endpoint of the study is a pathologically determined complete remission rate (pCR) of the disease locally and regionally. Secondly, the rate of sphincter preservation in low-sited tumours, overall downstaging rate,toxicity and survival parameters will be analysed.

Eligibility criteria: Inclusion Criteria:

* histologically verified adenocarcinoma of the rectum,
* resectable clinical stage II or III (IUCC TNM classification 2002);
* no prior radiotherapy and/or chemotherapy;
* World Health Organisation (WHO) performance status \< 2;
* age at diagnosis of 18 or older;
* and adequate bone marrow, liver, renal and cardiac function (no history of ischemic heart disease).

Exclusion Criteria:

* A history of prior malignancy other than non-melanoma skin cancer or in situ carcinoma of the cervix

Primary outcomes:
measure: complete pathological remission rate
timeFrame: 9 weeks
Secondary outcomes:
measure: the rate of sphincter preservation in low-sited tumours
timeFrame: 9 weeks
measure: toxicity of combined modality treatment (Number of Participants with Adverse Events)
timeFrame: 5 weeks
measure: overall downstaging rate
timeFrame: 9 weeks
measure: overall survival
timeFrame: 5 years
measure: local control
timeFrame: 5 years
measure: relapse-free survival
timeFrame: 5 years
measure: long-term rectal and urogenital morbidity
timeFrame: 2 years after the surgery
Other outcomes:
Locations:
city: Ljubljana
country: Slovenia
facility: Institute of Oncology
Study officials:
References:
citation: Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004 Oct 21;351(17):1731-40. doi: 10.1056/NEJMoa040694.
citation: Schuller J, Cassidy J, Dumont E, Roos B, Durston S, Banken L, Utoh M, Mori K, Weidekamm E, Reigner B. Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Cancer Chemother Pharmacol. 2000;45(4):291-7. doi: 10.1007/s002800050043.
citation: Kim JS, Kim JS, Cho MJ, Song KS, Yoon WH. Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2002 Oct 1;54(2):403-8. doi: 10.1016/s0360-3016(02)02856-0.
citation: Twelves C, Boyer M, Findlay M, Cassidy J, Weitzel C, Barker C, Osterwalder B, Jamieson C, Hieke K; Xeloda Colorectal Cancer Study Group. Capecitabine (Xeloda) improves medical resource use compared with 5-fluorouracil plus leucovorin in a phase III trial conducted in patients with advanced colorectal carcinoma. Eur J Cancer. 2001 Mar;37(5):597-604. doi: 10.1016/s0959-8049(00)00444-5.
citation: Jansman FG, Postma MJ, van Hartskamp D, Willemse PH, Brouwers JR. Cost-benefit analysis of capecitabine versus 5-fluorouracil/leucovorin in the treatment of colorectal cancer in the Netherlands. Clin Ther. 2004 Apr;26(4):579-89. doi: 10.1016/s0149-2918(04)90060-4.
citation: Dunst J, Reese T, Sutter T, Zuhlke H, Hinke A, Kolling-Schlebusch K, Frings S. Phase I trial evaluating the concurrent combination of radiotherapy and capecitabine in rectal cancer. J Clin Oncol. 2002 Oct 1;20(19):3983-91. doi: 10.1200/JCO.2002.02.049.
citation: Velenik V, Anderluh F, Oblak I, Strojan P, Zakotnik B. Capecitabine as a radiosensitizing agent in neoadjuvant treatment of locally advanced resectable rectal cancer: prospective phase II trial. Croat Med J. 2006 Oct;47(5):693-700.