Induction Chemotherapy,Radiochemotherapy, Consolidation Chemotherapy in Preoperative Treatment of Rectal Cancer

Rectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01489332
• Other study ID #: 163/06/11
• Status: Recruiting
• Phase: Phase 2
• First received: November 11, 2011
• Last updated: December 7, 2011
• Start date: October 2011
• Est. completion date: April 2018

Study information

• Verified date: December 2011
• Source: Institute of Oncology Ljubljana
• Contact: Vaneja Velenik, Prof.assist
• Phone: +386 1 5879297
• Email: vvelenik[@]onko-i.si
• Is FDA regulated: No
• Health authority: Slovenia: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: April 2018
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• intensified preoperative chemotherapy
capecitabine 1250 mg/m² p.o. twice daily for 14 consecutive days, 7 days rest for one cycle; radiotherapy: 50.4 Gy to the pelvis (25x 1.8 Gy on days 1-33, excluding weekends) plus 5.4 Gy on days 36-38 as a boost to the primary tumour (3 fractions of 1.8 Gy).Three- dimensional CT planing and a four field box technique with high energy photons (15 MV) will be used. capecitabine 825 mg/m² p.o. twice daily on days 1-38 (including weekends), One week after completion of radiochemotherapy patients receive 2 cycles of capecitabine based chemotherapy (1250 mg/m² p.o. twice daily for 14 consecutive days every three weeks). Radical surgery (TME): to be undertaken 8 weeks following completion of chemoradiation Postoperative treatment:capecitabine 1250 mg/m² p.o. twice daily for 14 consecutive days every three weeks; 3 cycles (R0 beginning 6-8 weeks after surgery

Locations

Country	Name	City	State
Slovenia	Institute of Oncology	Ljubljana

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Oncology Ljubljana

Country where clinical trial is conducted

Slovenia, 

References & Publications (6)

Bujko K, Glynne-Jones R, Bujko M. Adjuvant chemotherapy for rectal cancer. Ann Oncol. 2010 Dec;21(12):2443. doi: 10.1093/annonc/mdq616. — View 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):1743-50. doi: 10.1093/annonc/mdq054. Epub 2010 Mar 15. Review. — View 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. — View Citation

Habr-Gama A, Perez RO, Sabbaga J, Nadalin W, São Julião 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological complete remission rate (pCR)		after the pathological examination of surgical speciments ie within 14 days after the operation	No
Secondary	Toxicity	Number of patients with adverse events and the grade of adverse events	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)	Yes
Secondary	Histopathological R0 resection rate		after the pathological examination of resected speciments ie within 14 days after the operation	No
Secondary	Loco-regional failure rate		after 3y and 5y of operation	No
Secondary	Disease-free survival		after 3y and 5y of operation	No
Secondary	Overall survival		after 3y and 5y of the operation	No
Secondary	Quality of life	We will use EORTC questionnaires QLQ C30 and C38	before the treatment, after 1,and 3 years of the operation	No