Neuroendocrine CarcinomasPhase 2XELBEVOCTNCT01203306
Bevacizumab Plus Somatostatin Analogue and Metronomic Capecitabine in Patients With Advanced Neuroendocrine Tumors
A Phase 2 study testing bevacizumab + octreotide LAR + capecitabine in people with Neuroendocrine Carcinomas, run by University of Turin, Italy at 5 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Neuroendocrine Carcinomas
- What is being tested?
- bevacizumab + octreotide LAR + capecitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 5 sitesItaly
- Study dates
- Jan 2006to Dec 2010
- 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
- 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
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- 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
Who cannot join
- 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
Show all 10Show fewer
- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Italy5 sites, 2 recruiting
- Recruiting
Elisabetta Nobili
Bologna, Bologna, 40138
Elisabetta Nobili, MD, 051 6363 ext. 680, elisabetta.nobili3@unibo.it
Guido Biasco, MD, PhD
- Completed
Nicola Fazio
Milan, Milan, 20121
- Recruiting
Anna Ferrero
Orbassano, Turin, 10043
Anna Ferrero, MD, +39 011 9026 ext. 526, anna.ferrero80@libero.it
Maria P Brizzi, MD, PhD
- Completed
Lucia Tozzi
San Giovanni Rotondo, Foggia, 71013
- Completed
Enrica Milanesi
Turin, Turin, 10126
About this study
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
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.
Read the 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.
- Conditions
- Neuroendocrine Carcinomas
- Being tested
- bevacizumab + octreotide LAR + capecitabine
- Keywords
- bevacizumab, somatostatin analogue, metronomic capecitabine, neuroendocrine tumors
- Medical subject headings
- Carcinoma, Neuroendocrine, Neuroendocrine Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumab + octreotide LAR + capecitabineDrug
Also called Avastin, Sandostatin LAR, Xeloda
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
| Study group | Role | What they receive |
|---|---|---|
| Drugs: bevacizumab + octreotide LAR + capecitabine | Experimental | bevacizumab + octreotide + metronomic capecitabine Receives: Drug: bevacizumab + octreotide LAR + capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
time to progression
Measured: 36 months
Secondary outcomes (3)
Toxicity
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.
Measured: two years
Time to Treatment Failure (TTF)
TTF is the time from first day of treatment to the first occurrence of any adverse events with withdrew prematurely the treatment.
Measured: two years
Overall survival (OS)
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.
Measured: 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2010 (estimated)
- Study startJan 2006
- Primary completionMay 2009 (estimated)
- Study completionDec 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Neuroendocrine CarcinomasStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Turin, Italy
- Sponsor type
- University, hospital or other
- Investigators
- Alfredo Berruti, MD, PhD, Study director, Medical Oncology, Department of Clinical and Biological Sciences, University of Turin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01203306
- Sponsor's protocol ID
- EudraCT 2006-004748-22
- Acronym
- XELBEVOCT
- Status last verified
- Jul 2010
- First submitted
- 9 Sep 2010
- Last updated
- 16 Sep 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Brizzi MP, Berruti A, Ferrero A, Milanesi E, Volante M, Castiglione F, Birocco N, Bombaci S, Perroni D, Ferretti B, Alabiso O, Ciuffreda L, Bertetto O, Papotti M, Dogliotti L. Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte oncology network. BMC Cancer. 2009 Nov 3;9:388. doi: 10.1186/1471-2407-9-388.
PubMed 19886987Berruti A, Fazio N, Ferrero A, Brizzi MP, Volante M, Nobili E, Tozzi L, Bodei L, Torta M, D'Avolio A, Priola AM, Birocco N, Amoroso V, Biasco G, Papotti M, Dogliotti L. Bevacizumab plus octreotide and metronomic capecitabine in patients with metastatic well-to-moderately differentiated neuroendocrine tumors: the XELBEVOCT study. BMC Cancer. 2014 Mar 14;14:184. doi: 10.1186/1471-2407-14-184.
PubMed 24628963
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01203306
- Acronym / sponsor ID
- XELBEVOCT / EudraCT 2006-004748-22
- Conditions
- Neuroendocrine Carcinomas
- Keywords
- bevacizumab, somatostatin analogue, metronomic capecitabine, neuroendocrine tumors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- University of Turin, ItalyUniversity, hospital or other
- Study start
- Jan 2006
- Primary completion
- May 2009 (estimated)
- Study completion
- Dec 2010 (estimated)
- First posted
- 16 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Drugs: bevacizumab + octreotide LAR + capecitabine | Experimental | Drug: bevacizumab + octreotide LAR + capecitabinebevacizumab + octreotide + metronomic capecitabine |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bevacizumab + octreotide LAR + capecitabineAlso: Avastin, Sandostatin LAR, Xelodalong 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 | Drug | Drugs: bevacizumab + octreotide LAR + capecitabine |
Primary outcome
time to progression
Time frame: 36 months
3 secondary outcomes
Toxicity
Time frame: two years
Time to Treatment Failure (TTF)
Time frame: two years
Overall survival (OS)
Time frame: 48 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2010.
- Background: PubMed 19886987Brizzi MP, Berruti A, Ferrero A, Milanesi E, Volante M, Castiglione F, Birocco N, Bombaci S, Perroni D, Ferretti B, Alabiso O, Ciuffreda L, Bertetto O, Papotti M, Dogliotti L. Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte oncology network. BMC Cancer. 2009 Nov 3;9:388. doi: 10.1186/1471-2407-9-388.
- Derived from this study: PubMed 24628963Berruti A, Fazio N, Ferrero A, Brizzi MP, Volante M, Nobili E, Tozzi L, Bodei L, Torta M, D'Avolio A, Priola AM, Birocco N, Amoroso V, Biasco G, Papotti M, Dogliotti L. Bevacizumab plus octreotide and metronomic capecitabine in patients with metastatic well-to-moderately differentiated neuroendocrine tumors: the XELBEVOCT study. BMC Cancer. 2014 Mar 14;14:184. doi: 10.1186/1471-2407-14-184.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alfredo Berruti, MD, PhD study director
Medical Oncology, Department of Clinical and Biological Sciences, University of Turin
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing bevacizumab + octreotide LAR + capecitabine in people with Neuroendocrine Carcinomas, run by University of Turin, Italy at 5 sites in Italy.
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 12 inclusion and 10 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 16 Sep 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Italy. 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?
Contact Maria P Brizzi, MD, PhD (+39, 011-9026 ext. 007, mariapia.brizzi@email.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
time to progression (time frame: 36 months). 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 NCT01203306, which also lists 2 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 16 Sep 2010.