Clinical trial NCT01489332: Induction Chemotherapy,Radiochemotherapy, Consolidation Chemotherapy in Preoperative Treatment of Rectal Cancer
Official title: Induction Chemotherapy, Preoperative Radiochemotherapy, Consolidation Chemotherapy, Operation and Adjuvant Chemotherapy in the Treatment of Locally Advanced Rectal Cancer- OIGIT 5-01 Phase II Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: rectal cancer
capecitabine
radiotherapy
locally advanced rectal cancer
Lead sponsor: Institute of Oncology Ljubljana
Sponsor class: OTHER
First posted: 2011-12-09
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The use of capecitabine based preoperative chemoradiation and adjuvant chemotherapy is standard treatment of locally advanced rectal cancer. It has reduced local recurrence rate to less than 10%, but has only had limited effect on overall survival due to the constantly high (more than 30%) rate of distant metastasis.

Complete eradication of the primary tumour observed in the histopathological specimen (pathological complete response, pCR) correlates with a favourable overall prognosis so obtaining a pCR might be beneficial. The aim of the study is to investigate whether the addition of capecitabine based chemotherapy before preoperative chemoradiation and also before the operation improves pathological complete remission rate in locally advanced rectal cancer with acceptable toxicity. Secondary objectives are to evaluate pathological downstaging rate, histopathological R0 resection rate,sphincter preservation rate, perioperative surgical complication rate, local control, DFS, OS, late toxicity and quality of life.


Eligibility criteria: Inclusion Criteria:

* Male or female patients with histologically proven adenocarcinoma of the rectum (tumour located below the peritoneum),
* T3/4 or any node positive disease (clinical stage according the TNM classification system)
* No evidence of metastatic disease.
* The disease must be considered either resectable at the time of entry or thought to become resectable after preoperative chemoradiation.
* Age 18 years and more
* WHO Performance Status 0-2
* No prior radiotherapy, chemotherapy or any targeting therapy for rectal cancer
* Adequate hematological, hepatic and renal function Ability to swallow tablets
* Signed informed consent
* Patients must be willing and able to comply with the protocol for duration of the study

Exclusion Criteria:

* Malignancy of the rectum other than adenocarcinoma
* Any unrested synchronous colon cancer
* Other co-existing malignancy or malignancy within the past 5 years, with the exception of adequately treated in situ carcinoma of the cervix or basal cell carcinoma of the skin
* Significant heart disease (uncontrolled hypertension despite of medication (\> 150/100 mmHg), NYHA class III or IV heart disease,unstable angina or myocardial infarction within the past 1 year prior the study entry, history of significant ventricular arrhythmia requiring treatment)
* Pregnant or lactating patient
* Females with a positive or no pregnancy test unless childbearing potential can be otherwise excluded (amenorrheic for at least 2 years,hysterectomy or oophorectomy)

Primary outcomes:
measure: Pathological complete remission rate (pCR)
timeFrame: after the pathological examination of surgical speciments ie within 14 days after the operation
Secondary outcomes:
measure: Toxicity
timeFrame: According to NCI-CTC (version 3.0): every week for 16 week preoperative, perioperative (0-30 days postoperative), early (30 days - 6 months postoperative), and late (more than 6 months postoperative)
measure: Histopathological R0 resection rate
timeFrame: after the pathological examination of resected speciments ie within 14 days after the operation
measure: Loco-regional failure rate
timeFrame: after 3y and 5y of operation
measure: Disease-free survival
timeFrame: after 3y and 5y of operation
measure: Overall survival
timeFrame: after 3y and 5y of the operation
measure: Quality of life
timeFrame: before the treatment, after 1,and 3 years of the operation
Other outcomes:
Locations:
city: Ljubljana
country: Slovenia
facility: Institute of Oncology
Study officials:
affiliation: Institute of Oncology Ljubljana, Slovenia
name: Vaneja Velenik, Prof.assist
role: PRINCIPAL_INVESTIGATOR
References:
citation: Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U Jr, Silva e Sousa AH Jr, Campos FG, Kiss DR, Gama-Rodrigues J. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004 Oct;240(4):711-7; discussion 717-8. doi: 10.1097/01.sla.0000141194.27992.32.
citation: Velenik V, Oblak I, Anderluh F. Long-term results from a randomized phase II trial of neoadjuvant combined-modality therapy for locally advanced rectal cancer. Radiat Oncol. 2010 Sep 29;5:88. doi: 10.1186/1748-717X-5-88.
citation: Ruo L, Tickoo S, Klimstra DS, Minsky BD, Saltz L, Mazumdar M, Paty PB, Wong WD, Larson SM, Cohen AM, Guillem JG. Long-term prognostic significance of extent of rectal cancer response to preoperative radiation and chemotherapy. Ann Surg. 2002 Jul;236(1):75-81. doi: 10.1097/00000658-200207000-00012.
citation: Bujko K, Glynne-Jones R, Bujko M. Adjuvant chemotherapy for rectal cancer. Ann Oncol. 2010 Dec;21(12):2443. doi: 10.1093/annonc/mdq616. No abstract available.
citation: Bujko K, Glynne-Jones R, Bujko M. Does adjuvant fluoropyrimidine-based chemotherapy provide a benefit for patients with resected rectal cancer who have already received neoadjuvant radiochemotherapy? A systematic review of randomised trials. Ann Oncol. 2010 Sep;21(9):1743-1750. doi: 10.1093/annonc/mdq054. Epub 2010 Mar 15.
citation: Habr-Gama A, Perez RO, Sabbaga J, Nadalin W, Sao Juliao GP, Gama-Rodrigues J. Increasing the rates of complete response to neoadjuvant chemoradiotherapy for distal rectal cancer: results of a prospective study using additional chemotherapy during the resting period. Dis Colon Rectum. 2009 Dec;52(12):1927-34. doi: 10.1007/DCR.0b013e3181ba14ed.