Induction Chemotherapy,Radiochemotherapy, Consolidation Chemotherapy in Preoperative Treatment of Rectal Cancer - Full Text View

Purpose

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.

Condition	Intervention	Phase
Rectal Cancer	Drug: intensified preoperative chemotherapy	Phase 2

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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Capecitabine

U.S. FDA Resources

Further study details as provided by Institute of Oncology Ljubljana:

Primary Outcome Measures:

Pathological complete remission rate (pCR) [ Time Frame: after the pathological examination of surgical speciments ie within 14 days after the operation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Toxicity [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
Number of patients with adverse events and the grade of adverse events
Histopathological R0 resection rate [ Time Frame: after the pathological examination of resected speciments ie within 14 days after the operation ] [ Designated as safety issue: No ]
Loco-regional failure rate [ Time Frame: after 3y and 5y of operation ] [ Designated as safety issue: No ]
Disease-free survival [ Time Frame: after 3y and 5y of operation ] [ Designated as safety issue: No ]
Overall survival [ Time Frame: after 3y and 5y of the operation ] [ Designated as safety issue: No ]
Quality of life [ Time Frame: before the treatment, after 1,and 3 years of the operation ] [ Designated as safety issue: No ]
We will use EORTC questionnaires QLQ C30 and C38

Estimated Enrollment:	60
Study Start Date:	October 2011
Estimated Study Completion Date:	April 2018
Estimated Primary Completion Date:	April 2013 (Final data collection date for primary outcome measure)

Intervention Details:

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01489332

Contacts

Contact: Vaneja Velenik, Prof.assist	+386 1 5879297	vvelenik@onko-i.si
Contact: Franc Anderluh, MD	+386 1 5879297	fanderluh@onko/i.si

Locations

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

Sponsors and Collaborators

Institute of Oncology Ljubljana

Investigators

Principal Investigator:

Vaneja Velenik, Prof.assist

Institute of Oncology Ljubljana, Slovenia

More Information

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.

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.

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.

Bujko K, Glynne-Jones R, Bujko M. Adjuvant chemotherapy for rectal cancer. Ann Oncol. 2010 Dec;21(12):2443. 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):1743-50. Epub 2010 Mar 15. Review.

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.

Responsible Party:	Institute of Oncology Ljubljana
ClinicalTrials.gov Identifier:	NCT01489332 History of Changes
Other Study ID Numbers:	163/06/11
Study First Received:	November 11, 2011
Last Updated:	December 7, 2011
Health Authority:	Slovenia: Ethics Committee

Keywords provided by Institute of Oncology Ljubljana:

rectal cancer
capecitabine
radiotherapy
locally advanced rectal cancer

Additional relevant MeSH terms:

Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases

Intestinal Diseases
Rectal Diseases
Capecitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 23, 2013