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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2012 by Institute of Oncology Ljubljana.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Institute of Oncology Ljubljana
ClinicalTrials.gov Identifier:
NCT00842686
First received: February 11, 2009
Last updated: March 23, 2012
Last verified: March 2012
  Purpose

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 Intervention Phase
Locally Advanced Rectal Cancer
Drug: bevacizumab, capecitabine
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: Preoperative Radiotherapy With Capecitabine and Bevacizumab in Locally Advanced Rectal Cancer: CRAB Phase II Study

Resource links provided by NLM:


Further study details as provided by Institute of Oncology Ljubljana:

Primary Outcome Measures:
  • Pathological complete remission rate (pCR) [ Time Frame: after pathological examination of surgical speciments ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pathological response rate [ Time Frame: Toxicity/safety:during preoperative treatment, early and late postoperative follow up ] [ Designated as safety issue: Yes ]
  • Rate of sphincter sparing surgical procedure [ Time Frame: Toxicity/safety:during preoperative treatment, early and late postoperative follow up ] [ Designated as safety issue: Yes ]
  • Histopathological R0 resection rate [ Time Frame: Toxicity/safety:during preoperative treatment, early and late postoperative follow up ] [ Designated as safety issue: Yes ]
  • Acute and late toxicity [ Time Frame: Toxicity/safety:during preoperative treatment, early and late postoperative follow up ] [ Designated as safety issue: Yes ]
  • Loco-regional failure rate [ Time Frame: Toxicity/safety:during preoperative treatment, early and late postoperative follow up ] [ Designated as safety issue: Yes ]
  • Disease-free survival [ Time Frame: Toxicity/safety:during preoperative treatment, early and late postoperative follow up ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: Toxicity/safety:during preoperative treatment, early and late postoperative follow up ] [ Designated as safety issue: Yes ]
  • Quality of life [ Time Frame: Toxicity/safety:during preoperative treatment, early and late postoperative follow up ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: January 2009
Estimated Study Completion Date: August 2014
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
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
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

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
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 - 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00842686

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

Publications:

Responsible Party: Velenik Vaneja, MD, PhD, Institute of Oncolg Ljubljana, Slovenia
ClinicalTrials.gov Identifier: NCT00842686     History of Changes
Other Study ID Numbers: ML21901
Study First Received: February 11, 2009
Last Updated: March 23, 2012
Health Authority: Slovenia: Agency for Medicinal Products - Ministry of Health
Slovenia: Ethics Committee

Keywords provided by Institute of Oncology Ljubljana:
rectal cancer
capecitabine
bevacizumab
radiotherapy

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Bevacizumab
Capecitabine
Fluorouracil
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014