IMRT-SIB and Capecitabine in Preoperative Rectal Cancer Treatment

Rectal Carcinoma Clinical Trial

— BISER  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02268006
• Other study ID #: 41/12/13
• Status: Recruiting
• Phase: Phase 2
• First received: February 2, 2014
• Last updated: October 15, 2014
• Start date: January 2014
• Est. completion date: December 2020

Study information

• Verified date: September 2014
• Source: Institute of Oncology Ljubljana
• Contact: n/a
• Is FDA regulated: No
• Health authority: Slovenia: Institute of Oncology, KESOPKR
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 2020
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Rectal Carcinoma

Intervention

Radiation:
• IMRT-SIB

Drug:
• Capecitabine

Procedure:
• 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)

Arbea L, Ramos LI, Martínez-Monge R, Moreno M, Aristu J. Intensity-modulated radiation therapy (IMRT) vs. 3D conformal radiotherapy (3DCRT) in locally advanced rectal cancer (LARC): dosimetric comparison and clinical implications. Radiat Oncol. 2010 Feb 26;5:17. doi: 10.1186/1748-717X-5-17. — View Citation

Engels B, De Ridder M, Tournel K, Sermeus A, De Coninck P, Verellen D, Storme GA. Preoperative helical tomotherapy and megavoltage computed tomography for rectal cancer: impact on the irradiated volume of small bowel. Int J Radiat Oncol Biol Phys. 2009 Aug 1;74(5):1476-80. doi: 10.1016/j.ijrobp.2008.10.017. Epub 2009 Feb 21. — View Citation

Li JL, Ji JF, Cai Y, Li XF, Li YH, Wu H, Xu B, Dou FY, Li ZY, Bu ZD, Wu AW, Tham IW. Preoperative concomitant boost intensity-modulated radiotherapy with oral capecitabine in locally advanced mid-low rectal cancer: a phase II trial. Radiother Oncol. 2012 Jan;102(1):4-9. doi: 10.1016/j.radonc.2011.07.030. Epub 2011 Sep 6. — View Citation

Mok H, Crane CH, Palmer MB, Briere TM, Beddar S, Delclos ME, Krishnan S, Das P. Intensity modulated radiation therapy (IMRT): differences in target volumes and improvement in clinically relevant doses to small bowel in rectal carcinoma. Radiat Oncol. 2011 Jun 8;6:63. doi: 10.1186/1748-717X-6-63. — View Citation

Velenik V, Anderluh F, Oblak I, Strojan P, Zakotnik B. Capecitabine as a radiosensitizing agent in neoadjuvant treatment of locally advanced resectable rectal cancer: prospective phase II trial. Croat Med J. 2006 Oct;47(5):693-700. — 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 specimens i.e. within 14 days after the operation	No
Secondary	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)	Yes
Secondary	Histopathological R0 resection rate		after the pathological examination of resected specimens i.e. within 14 days after the operation	No
Secondary	Tumor down-staging rate		after the pathological examination of resected specimens i.e. within 14 days after the operation	No
Secondary	Rate of sphincter sparing surgical procedure		Toxicity/safety: one month after surgery.	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		before the treatment, after surgery, after1,2,3,4 and 5 years of the operation	No