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

NCT00842686 | Unknown Phase 2 DMC

• 1 other identifier: ML21901
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Locally Advanced Rectal Cancer

Keywords

rectal cancer; capecitabine; bevacizumab; radiotherapy

Outcome Measures

Primary Outcomes (1)

• Pathological complete remission rate (pCR)

  after pathological examination of surgical speciments

Secondary Outcomes (8)

• Pathological response rate

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

• Rate of sphincter sparing surgical procedure

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

• Histopathological R0 resection rate

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

• Acute and late toxicity

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

• Loco-regional failure rate

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

Interventions

bevacizumab, capecitabine DRUG

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)

Also known as: Avastin, Xeloda, radiation

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Institute of Oncology Ljubljana: lead

Study Sites (1)

Onstitute of Oncology, Zaloška 2

Ljubljana, 1000, Slovenia

Location

Related Publications (7)

• 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.

  PMID: 10944647 BACKGROUND

• 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.

  PMID: 15496622 BACKGROUND

• 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.

  PMID: 12351595 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 BACKGROUND

• 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.

  PMID: 17827451 BACKGROUND

• 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.

  PMID: 16258121 BACKGROUND

• 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.

  PMID: 17498568 BACKGROUND

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Bevacizumab; Capecitabine; Radiation

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Physical Phenomena

Study Officials

• Vaneja Velenik, MD, PhD

  Institute of Oncology, Ljubljana, Slovenia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 11, 2009
• First Posted: February 12, 2009
• Study Start: January 1, 2009
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2014
• Last Updated: March 26, 2012

Record last verified: 2012-03

Locations

SL (1)