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

Induction Chemotherapy, Preoperative Radiochemotherapy, Consolidation Chemotherapy, Operation and Adjuvant Chemotherapy in the Treatment of Locally Advanced Rectal Cancer- OIGIT 5-01 Phase II Trial

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.

Study Overview

• Status: Unknown
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: intensified preoperative chemotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Vaneja Velenik, Prof.assist; Phone Number: +386 1 5879297; Email: vvelenik@onko-i.si
• Study Contact Backup: Name: Franc Anderluh, MD; Phone Number: +386 1 5879297; Email: fanderluh@onko/i.si

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • Recruiting
    • Institute of Oncology
    • Contact: Franc Anderluh, MD; Phone Number: +386 1 5879297; Email: fanderluh@onko/i.si
    • Contact: Vaneja Velenik, Prof.assist; Phone Number: +386 1 5879297; Email: vvelenik@onko/i.si
    • Principal Investigator: Vaneja Velenik, Prof.assist
    • Sub-Investigator: Irena Oblak, Prof.assist
    • Sub-Investigator: Marija Skoblar Vidmar, MD
    • Sub-Investigator: Ajra Secerov Ermenc, MD
    • Sub-Investigator: Danijela Golo, MD
    • Sub-Investigator: Ibrahim Edhemovic, MD
    • Sub-Investigator: Mirko Omejc, Prof

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pathological complete remission rate (pCR)	after the pathological examination of surgical speciments ie within 14 days after the operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Loco-regional failure rate		after 3y and 5y of operation
Disease-free survival		after 3y and 5y of operation
Overall survival		after 3y and 5y of the operation
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)
Histopathological R0 resection rate		after the pathological examination of resected speciments ie within 14 days after the operation
Quality of life	We will use EORTC questionnaires QLQ C30 and C38	before the treatment, after 1,and 3 years of the operation

Collaborators and Investigators

• Sponsor: Institute of Oncology Ljubljana
• Investigators: Principal Investigator: Vaneja Velenik, Prof.assist, Institute of Oncology Ljubljana, Slovenia

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Anticipated): April 1, 2013
• Study Completion (Anticipated): April 1, 2018

Study Registration Dates

• First Submitted: November 11, 2011
• First Submitted That Met QC Criteria: December 7, 2011
• First Posted (Estimate): December 9, 2011

Study Record Updates

• Last Update Posted (Estimate): December 9, 2011
• Last Update Submitted That Met QC Criteria: December 7, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: capecitabine; radiotherapy; rectal cancer; locally advanced rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: 163/06/11