IMRT-SIB and Capecitabine in Preoperative Rectal Cancer Treatment

NCT02268006 | Unknown Phase 2

• 1 other identifier: 41/12/13
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Rectal Carcinoma

Keywords

rectal carcinoma; preoperative radiochemotherapy; IMRT; SIB

Outcome Measures

Primary Outcomes (1)

• Pathological complete remission rate (pCR)

  after the pathological examination of surgical specimens i.e. within 14 days after the operation

Secondary Outcomes (8)

• 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

Study Arms (1)

IMRT-SIB

OTHER

Radiation: IMRT-SIB; Drug: Capecitabine; Procedure: Surgery

Interventions

IMRT-SIB RADIATION

IMRT-SIB

Capecitabine DRUG

Also known as: (Xeloda, Capecitabine Teva, Ecansya)

IMRT-SIB

Surgery PROCEDURE

Also known as: Total Mesorectal Exscision

IMRT-SIB

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Institute of Oncology Ljubljana: lead

Study Sites (1)

Institute of Oncology

Ljubljana, 1000, Slovenia

RECRUITING

Related Publications (6)

• 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.

  PMID: 19231097 BACKGROUND

• Arbea L, Ramos LI, Martinez-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.

  PMID: 20187944 BACKGROUND

• 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.

  PMID: 21651775 BACKGROUND

• 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.

  PMID: 21903285 BACKGROUND

• 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.

  PMID: 17042060 RESULT

• 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.

  PMID: 20920276 RESULT

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Capecitabine; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2014
• First Posted: October 20, 2014
• Study Start: January 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2020
• Last Updated: October 20, 2014

Record last verified: 2014-09

Locations

SL (1)