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Bevacizumab Plus Somatostatin Analogue and Metronomic Capecitabine in Patients With Advanced Neuroendocrine Tumors (XELBEVOCT)

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: NCT01203306
Recruitment Status : Unknown
Verified July 2010 by University of Turin, Italy.
Recruitment status was:  Recruiting
First Posted : September 16, 2010
Last Update Posted : September 16, 2010
Information provided by:
University of Turin, Italy

Brief Summary:
Well differentiated neuroendocrine (NE) carcinomas have low proliferative activity and conventional chemotherapy is not recommended. Metronomic chemotherapy, i.e. the frequent administration of cytotoxic drugs at low doses, has demonstrated antiangiogenetic properties. Since well differentiated NE carcinomas are highly vascular, there is a rationale for testing metronomic chemotherapy and antiangiogenetic drugs. This is a national, multicenter, phase II study.

Condition or disease Intervention/treatment Phase
Neuroendocrine Carcinomas Drug: bevacizumab + octreotide LAR + capecitabine Phase 2

Detailed Description:

Metastatic or locally advanced well differentiated neuroendocrine carcinoma will be treated with a combination of bevacizumab (5 mg/kg) plus octreotide LAR (long- acting release) 20/30 mg plus capecitabine administered on a metronomic schedule (2000 mg/day).

Patients with stable disease, complete or partial response will continue treatment until progressive disease or unacceptable toxicity.

Primary endpoint: the response to treatment, evaluated according to the RECIST criteria.

Secondary endpoint: - toxicity, graded according to the NCI-CTG criteria;

  • symptomatic response: evaluated according to the changes in both the frequency and intensity of symptoms;
  • biochemical response: evaluated considering the changes in the tumor marker levels (circulating Chromogranin A);
  • relationship between vascular endothelial growth factor (VEGF) polymorphisms and response to treatment;
  • time to progression and survival: measured from the date of treatment start to the date of progression and the date of last follow-up or death, respectively.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of the Combination of Bevacizumab Plus Somatostatin Analogue and Metronomic Capecitabine in Patients With Advanced Inoperable Well-Differentiated Neuroendocrine Tumors
Study Start Date : January 2006
Estimated Primary Completion Date : May 2009
Estimated Study Completion Date : December 2010

Arm Intervention/treatment
Experimental: Drugs: bevacizumab + octreotide LAR + capecitabine
bevacizumab + octreotide + metronomic capecitabine
Drug: bevacizumab + octreotide LAR + capecitabine
long acting octreotide acetate at a dose of 20 or 30 mg administered intramuscularly every 4 weeks; Bevacizumab at a dose of 5 mg/kg every 2 weeks; orally capecitabine administered at a dose of 2000 mg/daily
Other Names:
  • Avastin
  • Sandostatin LAR
  • Xeloda

Primary Outcome Measures :
  1. time to progression [ Time Frame: 36 months ]

Secondary Outcome Measures :
  1. Toxicity [ Time Frame: two years ]
    All adverse events encountered during the clinical study will be reported. The intensity of clinical adverse events will be graded according to the NCI Common Toxicity Criteria (CTC) version 3.0 grading system.

  2. Time to Treatment Failure (TTF) [ Time Frame: two years ]
    TTF is the time from first day of treatment to the first occurrence of any adverse events with withdrew prematurely the treatment.

  3. Overall survival (OS) [ Time Frame: 48 months ]
    Overall survival (OS) will be computed as the time between the first day of treatment and the date of death or the last date the patient was known to be alive.

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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:

  • Histologically or cytologically diagnosis of well-differentiated neuroendocrine carcinoma
  • Inoperable disease
  • Age > 18
  • ECOG Performance Status 0-2
  • Life expectancy of at least 12 weeks
  • Measurable and/or evaluable lesions according to RECIST criteria
  • Radiological documentation of disease progression
  • Adequate bone marrow reserve
  • Adequate hepatic and renal function
  • Urine dipstick of proteinuria < 2+
  • Written informed consent
  • Comply with the protocol procedures

Exclusion criteria:

  • Serious non-healing wound or ulcer
  • Evidence of bleeding diathesis or coagulopathy
  • Uncontrolled hypertension
  • Clinically significant cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication
  • Current or recent ongoing treatment with anticoagulants for therapeutic purposes
  • Chronic, daily treatment with high-dose aspirin (>325 mg/day) or other medications known to predispose to gastrointestinal ulceration
  • Patients with severe renal impairment (creatinine clearance below 30 ml/min)
  • Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study
  • Pregnant or lactating women.

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): NCT01203306

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Contact: Maria P Brizzi, MD, PhD +39, 011-9026 ext 007

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Lucia Tozzi Completed
San Giovanni Rotondo, Foggia, Italy, 71013
Anna Ferrero Recruiting
Orbassano, Turin, Italy, 10043
Contact: Anna Ferrero, MD    +39 011 9026 ext 526   
Sub-Investigator: Maria P Brizzi, MD, PhD         
Elisabetta Nobili Recruiting
Bologna, Italy, 40138
Contact: Elisabetta Nobili, MD    051 6363 ext 680   
Principal Investigator: Guido Biasco, MD, PhD         
Nicola Fazio Completed
Milan, Italy, 20121
Enrica Milanesi Completed
Turin, Italy, 10126
Sponsors and Collaborators
University of Turin, Italy
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Study Director: Alfredo Berruti, MD, PhD Medical Oncology, Department of Clinical and Biological Sciences, University of Turin
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Alfredo Berruti, Dipartimento di Scienze Cliniche e Biologiche - Università di Torino Identifier: NCT01203306    
Other Study ID Numbers: EudraCT 2006-004748-22
First Posted: September 16, 2010    Key Record Dates
Last Update Posted: September 16, 2010
Last Verified: July 2010
Keywords provided by University of Turin, Italy:
somatostatin analogue
metronomic capecitabine
neuroendocrine tumors
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Carcinoma, Neuroendocrine
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplasms, Glandular and Epithelial
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
Gastrointestinal Agents
Antineoplastic Agents, Hormonal