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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2010 by University of Turin, Italy.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
University of Turin, Italy
ClinicalTrials.gov Identifier:
NCT01203306
First received: September 9, 2010
Last updated: September 15, 2010
Last verified: July 2010
  Purpose

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 Intervention Phase
Neuroendocrine Carcinomas
Drug: bevacizumab + octreotide LAR + capecitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Turin, Italy:

Primary Outcome Measures:
  • time to progression [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Toxicity [ Time Frame: two years ] [ Designated as safety issue: Yes ]
    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.

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

  • Overall survival (OS) [ Time Frame: 48 months ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 42
Study Start Date: January 2006
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT01203306

Contacts
Contact: Maria P Brizzi, MD, PhD +39, 011-9026 ext 007 mariapia.brizzi@email.it

Locations
Italy
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    anna.ferrero80@libero.it   
Sub-Investigator: Maria P Brizzi, MD, PhD         
Elisabetta Nobili Recruiting
Bologna, Italy, 40138
Contact: Elisabetta Nobili, MD    051 6363 ext 680    elisabetta.nobili3@unibo.it   
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
Investigators
Study Director: Alfredo Berruti, MD, PhD Medical Oncology, Department of Clinical and Biological Sciences, University of Turin
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Alfredo Berruti, Dipartimento di Scienze Cliniche e Biologiche - Università di Torino
ClinicalTrials.gov Identifier: NCT01203306     History of Changes
Other Study ID Numbers: EudraCT 2006-004748-22
Study First Received: September 9, 2010
Last Updated: September 15, 2010
Health Authority: Italy: AIFA - The Italian Medicines Agency

Keywords provided by University of Turin, Italy:
bevacizumab
somatostatin analogue
metronomic capecitabine
neuroendocrine tumors

Additional relevant MeSH terms:
Carcinoma, Neuroendocrine
Neuroendocrine Tumors
Adenocarcinoma
Carcinoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Bevacizumab
Capecitabine
Fluorouracil
Octreotide
Somatostatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Gastrointestinal Agents
Growth Inhibitors
Growth Substances
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 20, 2014