BISER: IMRT-SIB and Capecitabine in Preoperative Rectal Cancer Treatment

Sponsor

Institute of Oncology Ljubljana (Other)

Overall Status

Unknown status

CT.gov ID

NCT02268006

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Using small radiation beamlets of different intensity, IMRT (intensity modulated radiation therapy) allows shaping the dose around planning target volume with better sparing of normal tissue comparing to 3D conformal radiotherapy. It allows daily delivery of higher dose to the tumor with simultaneous integrated boost (SIB), consequently shortening total treatment time with potentially better response to treatment. In advanced rectal adenocarcinoma excellent response to preoperative radiochemotherapy with complete eradication of the primary tumor observed in the histopathological specimen (pathological complete response, pCR) correlates with a favorable overall prognosis, so trying to achieve better response to preoperative treatment with higher pCR seams feasible.

PURPOSE:The hypothesis of this study is that in preoperative radiochemotherapy for locally advanced rectal adenocarcinoma shortening of the total treatment time with IMRT-SIB to 22 daily fractions concomitant with capecitabine results in an improved pCR rate from 9% (Slovenian trial) to 25%. Secondary objectives are to evaluate pathological down-staging rate, histopathological R0 resection rate, sphincter preservation rate, perioperative surgical complication rate, local control, disease-free survival (DFS), overall survival (OS), late toxicity and quality of life.

Condition or Disease	Intervention/Treatment	Phase
Rectal Carcinoma	Radiation: IMRT-SIB Drug: Capecitabine Procedure: Surgery	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Preoperative Radiochemotherapy With IMRT - Simultaneous Integrated Boost in Locally Advanced Rectal Cancer - BISER

Study Start Date :

Jan 1, 2014

Anticipated Primary Completion Date :

Dec 1, 2015

Anticipated Study Completion Date :

Dec 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Other: IMRT-SIB	Radiation: IMRT-SIB Drug: Capecitabine Other Names: (Xeloda, Capecitabine Teva, Ecansya) Procedure: Surgery Other Names: Total Mesorectal Exscision

Arm

Intervention/Treatment

Other: IMRT-SIB

Radiation: IMRT-SIB

Drug: Capecitabine

Other Names:

(Xeloda, Capecitabine Teva, Ecansya)

Procedure: Surgery

Other Names:

Total Mesorectal Exscision

Outcome Measures

Primary Outcome Measures

Pathological complete remission rate (pCR) [after the pathological examination of surgical specimens i.e. within 14 days after the operation]

Secondary Outcome Measures

Toxicity [According to NCI-CTC (version 4.0): 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 specimens i.e. within 14 days after the operation]
Tumor down-staging rate [after the pathological examination of resected specimens i.e. within 14 days after the operation]
Rate of sphincter sparing surgical procedure [Toxicity/safety: one month after surgery.]
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]
Quality of life [before the treatment, after surgery, after1,2,3,4 and 5 years of the operation]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Biopsy-proven newly diagnosed primary rectal adenocarcinoma
Locally advanced tumor fulfilling at least one of the following criteria on pelvic

MRI:

T ≥ 3 or
N ≥ 1
Positive mesorectal fascia (MRF), i.e. tumor or lymph node one mm or less from the mesorectal fascia
Tumor located od 0 - 15 cm above anocutaneous junction or below peritoneum
Age 18 years and more
Signed informed consent
WHO Performance Status 0-2
Patients is considered to be mentally and physically ft for chemotherapy as judged by oncologist
Adequate hematological, hepatic and renal function (WBC ≥ 3.0 x 109/L, neu ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, renal clearance ≥ 50 ml/min, bilirubin ≤ 3x normal value, aspartate transaminase/alanine transaminase (AST/ALT) ≤ 2,5x normal value)

Exclusion Criteria:

T4 inoperable tumor - extensive growth into cranial part of the sacrum (above S3) or the lumbosacral nerve roots
Metastatic or recurrent rectal 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
Chronic bowel inflammatory disease
Pregnant or lactating patient
Significant heart disease (uncontrolled hypertension despite of medication (> 150/100 mmHg), New York Heart Association (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)
Inability to consciously sign the consent form due to physical or psychological disabilities