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A Phase II Study of Capecitabine, Oxaliplatin and Bevacizumab for Metastatic or Unresectable Neuroendocrine Tumors

Phase 2
18 Years
Open (Enrolling)
Neuroendocrine Tumors

Thank you

Trial Information

A Phase II Study of Capecitabine, Oxaliplatin and Bevacizumab for Metastatic or Unresectable Neuroendocrine Tumors


1. Determine an estimation of median time to progression (TTP) for patients treated with
bevacizumab in combination with capecitabine and oxaliplatin

2. Assess the toxicities associated with this regimen


1. Determine objective response rate (RR) for patients treated with this regimen

2. Conduct exploratory analyses of efficacy according to degree of tumor differentiation
and primary location

3. Determine utility of biochemical markers as a surrogate endpoint for tumor response

Inclusion Criteria:

Subjects must be treated at Stanford University Medical Center for the
entire length of study participation.

- Patients must have histologically or cytologically confirmed neuroendocrine tumor,
including both well-differentiated tumors (carcinoid) or moderately to poorly
differentiated tumors. Patients must be deemed unresectable due to involvement of
critical vasculature, adjacent organ invasion, or presence of metastasis.

- Patients with prior surgical resection who develop radiological or clinical evidence
of metastatic cancer do not require separate histological or cytological confirmation
of metastatic disease unless an interval of > 5 years has elapsed between the primary
surgery and the development of metastatic disease. Clinicians should consider biopsy
of lesions to establish diagnosis of metastatic disease if there is substantial
clinical ambiguity regarding the nature or source of apparent metastases.

- Prior chemotherapy will be permitted, although the patient may not have had prior

- Patients must have a primary or metastatic lesion measurable in at least one
dimension by Modified RECIST criteria (see Section 4.2) within 4 weeks prior to entry
of study

- Patients must have ECOG performance status of 0-2

- Patients must be >= 18 years of age

- Laboratory values <= 2 weeks prior to randomization:

- Absolute Neutrophil Count (ANC) >=1500/mm3

- Platelets (PLT) >= 100,000/mm3

- Hemoglobin (Hgb) >= 9 g/dL

- Serum creatinine <= 1.5 x ULN

- Serum bilirubin <= 1.5 x ULN (<= 3.0 x ULN if liver metastases present)

- Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), and
alkaline phosphatase <= 3.0 x ULN (<= 5.0 x ULN if liver metastases present).
Note: ERCP or percutaneous stenting may be used to normalize the liver function

- Life expectancy >= 12 weeks

- Ability to give written informed consent according to local guidelines

Exclusion Criteria:- Disease-Specific Exclusions

1. Prior oxaliplatin for any reason.

2. Prior full field radiotherapy <= 4 weeks or limited field radiotherapy <= 2 weeks
prior to enrollment. Patients must have recovered from all therapy-related
toxicities. The site of previous radiotherapy should have evidence of progressive
disease if this is the only site of disease.

3. Prior biologic or immunotherapy <= 2 weeks prior to registration. Patients must have
recovered from all therapy-related toxicities

4. Prior therapy with anti-VEGF agents

5. If history of other primary cancer, subject will be eligible only if she or he has:

- Curatively resected non-melanomatous skin cancer

- Curatively treated cervical carcinoma in situ

- Other primary solid tumor curatively treated with no known active disease
present and no treatment administered for the last 3 years

6. Concurrent use of other investigational agents and patients who have received
investigational drugs <= 4 weeks prior to enrollment.

- General Medical Exclusions

1. Subjects known to have chronic or active hepatitis B or C infection 2. History of any
medical or psychiatric condition or laboratory abnormality that in the opinion of the
investigator may increase the risks associated with study participation or study drug
administration or may interfere with the conduct of the study or interpretation of study
results 3. Male subject who is not willing to use adequate contraception upon enrollment
into this study and for 6 months following the last dose of second-line treatment 4.
Female subject (of childbearing potential, post-menopausal for less than 6 months, not
surgically sterilized, or not abstinent) who is not willing to use an oral, patch or
implanted contraceptive, double-barrier birth control, or an IUD during the course of the
study and for 6 months following the last dose of second-line treatment 5. Female subject
who is breast-feeding or who has positive serum pregnancy test 72 hours prior to
randomization 6. Pleural effusion or ascites that causes respiratory compromise (>= CTCAE
grade 2 dyspnea) 7. Any of the following concurrent severe and/or uncontrolled medical
conditions within 24 weeks of enrollment which could compromise participation in the

- Unstable angina pectoris

- Symptomatic congestive heart failure

- Myocardial infarction <= 6 months prior to registration and/or randomization

- Serious uncontrolled cardiac arrhythmia

- Uncontrolled diabetes

- Active or uncontrolled infection

- Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the

- Chronic renal disease

- Acute or chronic liver disease (e.g., hepatitis, cirrhosis) 8. Patients unwilling to
or unable to comply with the protocol 9. Life expectancy of less than 12 weeks 10.
Current, recent (within 4 weeks of the first infusion of this study), or planned
participation in an experimental drug study other than a Genentech-sponsored
bevacizumab cancer study

- Bevacizumab-Specific Exclusions

1. Inadequately controlled hypertension (defined as systolic blood pressure >
150 and/or diastolic blood pressure > 100 mmHg on antihypertensive

2. Any prior history of hypertensive crisis or hypertensive encephalopathy

3. New York Heart Association (NYHA) Grade II or greater congestive heart
failure (see Appendix E)

4. History of myocardial infarction or unstable angina within 6 months prior
to study enrollment

5. History of stroke or transient ischemic attack within 6 months prior to
study enrollment

6. Known CNS disease

7. Significant vascular disease (e.g., aortic aneurysm, aortic dissection)

8. Symptomatic peripheral vascular disease

9. Evidence of bleeding diathesis or coagulopathy

10. Major surgical procedure, open biopsy, or significant traumatic injury
within 28 days prior to study enrollment or anticipation of need for major
surgical procedure during the course of the study

11. Core biopsy or other minor surgical procedure, excluding placement of a
vascular access device, within 7 days prior to study enrollment

12. History of abdominal fistula, gastrointestinal perforation, or
intra-abdominal abscess within 6 months prior to study enrollment

13. Serious, non-healing wound, ulcer, or bone fracture

14. Urine protein >= 2+ on urinalysis dipstick and >= 1.0 gram on 24-hour urine

15. Known hypersensitivity to any component of bevacizumab

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Time to progression will be the primary outcome measure for this trial.

Outcome Time Frame:

assessed every 3 months by RECIST

Safety Issue:


Principal Investigator

George Albert Fisher M.D. Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Stanford University


United States: Food and Drug Administration

Study ID:




Start Date:

November 2006

Completion Date:

February 2013

Related Keywords:

  • Neuroendocrine Tumors
  • Neuroendocrine Tumors



Stanford University School of Medicine Stanford, California  94305-5317