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

Primary Purpose

Locally Advanced Rectal Cancer

Status

Unknown status

Phase

Phase 2

Locations

Slovenia

Study Type

Interventional

Intervention

bevacizumab, capecitabine

About this trial

This is an interventional treatment trial for Locally Advanced Rectal Cancer focused on measuring rectal cancer, capecitabine, bevacizumab, radiotherapy

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Onstitute of Oncology, Zaloška 2

Outcomes

Primary Outcome Measures

Pathological complete remission rate (pCR)

Secondary Outcome Measures

Pathological response rate

Rate of sphincter sparing surgical procedure

Histopathological R0 resection rate

Acute and late toxicity

Loco-regional failure rate

Disease-free survival

Overall survival

Quality of life

Full Information

NCT ID

NCT00842686

First Posted

February 11, 2009

Last Updated

March 23, 2012

Sponsor

Institute of Oncology Ljubljana

1. Study Identification

Unique Protocol Identification Number

NCT00842686

Brief Title

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

Acronym

CRAB

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2012

Overall Recruitment Status

Unknown status

Study Start Date

January 2009 (undefined)

Primary Completion Date

August 2010 (Actual)

Study Completion Date

August 2014 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor

Institute of Oncology Ljubljana

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Locally Advanced Rectal Cancer

Keywords

rectal cancer, capecitabine, bevacizumab, radiotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

bevacizumab, capecitabine

Other Intervention Name(s)

Avastin, Xeloda, radiation

Intervention Description

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)

Primary Outcome Measure Information:

Title

Pathological complete remission rate (pCR)

Time Frame

after pathological examination of surgical speciments

Secondary Outcome Measure Information:

Title

Pathological response rate

Time Frame