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Preoperative Radiotherapy With Capecitabine and Bevacizumab in Locally Advanced Rectal Cancer: CRAB Phase II Study (CRAB)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00842686
Recruitment Status : Unknown
Verified March 2012 by Institute of Oncology Ljubljana.
Recruitment status was:  Active, not recruiting
First Posted : February 12, 2009
Last Update Posted : March 26, 2012
Information provided by:
Institute of Oncology Ljubljana

Brief Summary:

The use of preoperative chemoradiation and adjuvant chemotherapy with 5-FU based chemotherapy 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.

However, it has been shown that 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 bevacizumab to preoperative fluoropyrimidinebased chemoradiation 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 or disease Intervention/treatment Phase
Locally Advanced Rectal Cancer Drug: bevacizumab, capecitabine Phase 2

Detailed Description:
  • radiotherapy: 45 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. All fields will be treated daily. Multileaf collimators will be used to shape individual radiation fields. Patients will be irradiated in a prone position with a full bladder and by using belly board to minimize exposure of the small bowel.
  • capecitabine 825 mg/m² p.o. twice daily on days 1-38 (including weekends),
  • bevacizumab: at dose 5 mg/kg on days -14, 2, 16,30.
  • Radical surgery (TME): to be undertaken ideally 6-8 weeks following completion of chemoradiation.

Postoperative treatment (in patients achieving histopathological R0 or R1 resection):capecitabine 1250 mg/m² p.o. twice daily for 14 consecutive days every three weeks; 4 cycles (R0)or 6 cycles (R1) beginning 6-8 weeks after surgery

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Preoperative Radiotherapy With Capecitabine and Bevacizumab in Locally Advanced Rectal Cancer: CRAB Phase II Study
Study Start Date : January 2009
Actual Primary Completion Date : August 2010
Estimated Study Completion Date : August 2014

Resource links provided by the National Library of Medicine

Intervention Details:
  • Drug: bevacizumab, capecitabine
    bevacizumab 5mg/kg days -15,1,15,29 capecitabine 1250 mg/square m/day during radiotherapy radiotherapy 50,4 Gy (1,8 Gy per fraction)
    Other Names:
    • Avastin
    • Xeloda
    • radiation

Primary Outcome Measures :
  1. Pathological complete remission rate (pCR) [ Time Frame: after pathological examination of surgical speciments ]

Secondary Outcome Measures :
  1. Pathological response rate [ Time Frame: Toxicity/safety:during preoperative treatment, early and late postoperative follow up ]
  2. Rate of sphincter sparing surgical procedure [ Time Frame: Toxicity/safety:during preoperative treatment, early and late postoperative follow up ]
  3. Histopathological R0 resection rate [ Time Frame: Toxicity/safety:during preoperative treatment, early and late postoperative follow up ]
  4. Acute and late toxicity [ Time Frame: Toxicity/safety:during preoperative treatment, early and late postoperative follow up ]
  5. Loco-regional failure rate [ Time Frame: Toxicity/safety:during preoperative treatment, early and late postoperative follow up ]
  6. Disease-free survival [ Time Frame: Toxicity/safety:during preoperative treatment, early and late postoperative follow up ]
  7. Overall survival [ Time Frame: Toxicity/safety:during preoperative treatment, early and late postoperative follow up ]
  8. Quality of life [ Time Frame: Toxicity/safety:during preoperative treatment, early and late postoperative follow up ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 - 80 years
  • 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)
  • Serious, non-healing wound, ulcer or bone fracture
  • Evidence of active peptic ulcer or upper GI bleeding
  • Evidence of bleeding diathesis or coagulopathy
  • Chronic daily treatment with high-dose aspirin(>325mg/day)
  • Current or recent (>10 days) use of full-dose of parenteral anticoagulants or thrombolytic agents for therapeutic purpose
  • Patients receiving a concomitant treatment with drugs interacting with capecitabine such as flucitosine, phenytoin, or warfarin
  • Known dihydropyrimidine dehydrogenase (DPD)deficiency
  • Major surgery within 4 weeks prior to study treatment starts, or lack of complete recovery from the effects of major surgery or open biopsy
  • Known hypersensitivity to biological drugs
  • Treatment with any investigational drug within 30 days before beginning treatment with the study drug
  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00842686

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Onstitute of Oncology, Zaloška 2
Ljubljana, Slovenia, 1000
Sponsors and Collaborators
Institute of Oncology Ljubljana
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Principal Investigator: Vaneja Velenik, MD, PhD Institute of Oncology, Ljubljana, Slovenia

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Responsible Party: Velenik Vaneja, MD, PhD, Institute of Oncolg Ljubljana, Slovenia Identifier: NCT00842686    
Other Study ID Numbers: ML21901
First Posted: February 12, 2009    Key Record Dates
Last Update Posted: March 26, 2012
Last Verified: March 2012
Keywords provided by Institute of Oncology Ljubljana:
rectal cancer
Additional relevant MeSH terms:
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Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action