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Locally Advanced Rectal CancerPhase 2CRABNCT00842686

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

A Phase 2 study testing bevacizumab, capecitabine in people with Locally Advanced Rectal Cancer, run by Institute of Oncology Ljubljana at 1 site in Slovenia.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Locally Advanced Rectal Cancer
What is being tested?
bevacizumab, capecitabine
How many people
60 participants
Where
1 siteSlovenia
Study dates
Jan 2009to Aug 2014
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 9Show fewer
  • 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

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

1 site in 1 country.

Slovenia1 site

  • Onstitute of Oncology, Zaloška 2

    Ljubljana, 1000

Other trials in Slovenia

About this study

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.

Read the 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

Being tested
bevacizumab, capecitabine
Keywords
rectal cancer, capecitabine, bevacizumab, radiotherapy
Medical subject headings
Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • bevacizumab, capecitabineDrug

    Also called Avastin, Xeloda, radiation

    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)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pathological complete remission rate (pCR)

    Measured: after pathological examination of surgical speciments

Secondary outcomes (8)

  1. Pathological response rate

    Measured: Toxicity/safety:during preoperative treatment, early and late postoperative follow up

  2. Rate of sphincter sparing surgical procedure

    Measured: Toxicity/safety:during preoperative treatment, early and late postoperative follow up

  3. Histopathological R0 resection rate

    Measured: Toxicity/safety:during preoperative treatment, early and late postoperative follow up

  4. Acute and late toxicity

    Measured: Toxicity/safety:during preoperative treatment, early and late postoperative follow up

  5. Loco-regional failure rate

    Measured: Toxicity/safety:during preoperative treatment, early and late postoperative follow up

  6. Disease-free survival

    Measured: Toxicity/safety:during preoperative treatment, early and late postoperative follow up

  7. Overall survival

    Measured: Toxicity/safety:during preoperative treatment, early and late postoperative follow up

  8. Quality of life

    Measured: Toxicity/safety:during preoperative treatment, early and late postoperative follow up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Feb 2009 (estimated)
  2. Study startJan 2009
  3. Primary completionAug 2010
  4. Study completionAug 2014 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00842686
Sponsor's protocol ID
ML21901
Acronym
CRAB
Status last verified
Mar 2012
First submitted
11 Feb 2009
Last updated
26 Mar 2012
Results posted
No
Data monitoring committee
Yes

Publications

  • Camma C, Giunta M, Fiorica F, Pagliaro L, Craxi A, Cottone M. Preoperative radiotherapy for resectable rectal cancer: A meta-analysis. JAMA. 2000 Aug 23-30;284(8):1008-15. doi: 10.1001/jama.284.8.1008.

    PubMed 10944647

  • Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004 Oct 21;351(17):1731-40. doi: 10.1056/NEJMoa040694.

    PubMed 15496622

  • Dunst J, Reese T, Sutter T, Zuhlke H, Hinke A, Kolling-Schlebusch K, Frings S. Phase I trial evaluating the concurrent combination of radiotherapy and capecitabine in rectal cancer. J Clin Oncol. 2002 Oct 1;20(19):3983-91. doi: 10.1200/JCO.2002.02.049.

    PubMed 12351595

  • 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.

    PubMed 17042060

  • Duda DG, Jain RK, Willett CG. Antiangiogenics: the potential role of integrating this novel treatment modality with chemoradiation for solid cancers. J Clin Oncol. 2007 Sep 10;25(26):4033-42. doi: 10.1200/JCO.2007.11.3985.

    PubMed 17827451

  • Willett CG, Boucher Y, Duda DG, di Tomaso E, Munn LL, Tong RT, Kozin SV, Petit L, Jain RK, Chung DC, Sahani DV, Kalva SP, Cohen KS, Scadden DT, Fischman AJ, Clark JW, Ryan DP, Zhu AX, Blaszkowsky LS, Shellito PC, Mino-Kenudson M, Lauwers GY. Surrogate markers for antiangiogenic therapy and dose-limiting toxicities for bevacizumab with radiation and chemotherapy: continued experience of a phase I trial in rectal cancer patients. J Clin Oncol. 2005 Nov 1;23(31):8136-9. doi: 10.1200/JCO.2005.02.5635. No abstract available.

    PubMed 16258121

  • Czito BG, Bendell JC, Willett CG, Morse MA, Blobe GC, Tyler DS, Thomas J, Ludwig KA, Mantyh CR, Ashton J, Yu D, Hurwitz HI. Bevacizumab, oxaliplatin, and capecitabine with radiation therapy in rectal cancer: Phase I trial results. Int J Radiat Oncol Biol Phys. 2007 Jun 1;68(2):472-8. doi: 10.1016/j.ijrobp.2007.02.001.

    PubMed 17498568

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing bevacizumab, capecitabine in people with Locally Advanced Rectal Cancer, run by Institute of Oncology Ljubljana at 1 site in Slovenia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 26 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Slovenia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological complete remission rate (pCR) (time frame: after pathological examination of surgical speciments). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00842686, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2012.

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