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Capecitabine, Temozolomide, and Bevacizumab for Metastatic or Unresectable Pancreatic Neuroendocrine Tumors
Not Recruiting
Trial ID: NCT01525082
Purpose
The purpose of this research is to evaluate the effectiveness and safety of a combination of
capecitabine, temozolomide and bevacizumab in the treatment of advanced pancreatic
neuroendocrine tumors.
Official Title
A Phase 2 Study of Capecitabine, Temozolomide, and Bevacizumab for Metastatic or Unresectable Pancreatic Neuroendocrine Tumors
Stanford Investigator(s)
Shagufta Shaheen
Clinical Assistant Professor, Medicine - Oncology
George A. Fisher Jr.
Colleen Haas Chair in the School of Medicine
Eligibility
INCLUSION CRITERIA
- Histologically-confirmed pancreatic neuroendocrine tumors that are moderately- or
well-differentiated
- Metastatic or unresectable disease
- If prior surgical resection > 5 years before the development of metastatic disease, a
separate (recent) histological or cytological confirmation of metastatic disease is
required
- If there is substantial clinical ambiguity regarding the nature or source of apparent
metastases, clinicians should consider biopsy of lesions to establish diagnosis of
metastatic disease
- The site of previous radiotherapy, if the only site of disease, has evidence of
progressive disease
- If prior sunitinib and everolimus has been administered, a 2-week wash-out period is
required prior to 1st dose on this study
- If prior liver-directed therapies (ie, chemoembolization, radioembolization), target
lesions in the liver have demonstrated growth since the liver-directed treatment
- If prior peptide receptor radionuclide therapy (PRRT), target lesions in the liver
have demonstrated growth since the liver-directed treatment
- Low-dose aspirin (≤ 325 mg/d) may be continued in subjects at higher risk for arterial
thromboembolic disease.
- Primary or metastatic tumor lesion measurable in at least 1 dimension, within 4 weeks
prior to entry of study.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- ≥ 18 years of age.
- Laboratory values as follows, ≤ 2 weeks prior to randomization:
- Absolute neutrophil count (ANC) ≥ 1.5 x 10e9/L (≥ 1500/mm³)
- Platelets (PLT) ≥ 100 x 10e9/L (≥ 100,000/mm³)
- Hemoglobin (Hgb) ≥ 9 g/dL
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
- Serum bilirubin ≤ 1.5 x ULN
- Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) ≤ 3.0 x ULN
(≤ 5.0 x ULN if liver metastases present). Note: endoscopic retrograde
cholangiopancreatography (ERCP) or percutaneous stenting may be used to normalize the
liver function tests
- Urine dipstick or urinalysis for protein, value must be 0, trace, or 1+ protein to
enroll. EXCEPTION: if ≥ 2+ must check 24-hour urine protein and must be < 1 g
- Life expectancy ≥ 12 weeks
- Ability to give written informed consent according to local guidelines
- If any prior therapy-related toxicities, must have recovered from all
EXCLUSION CRITERIA Disease-Specific Exclusions
- Prior bevacizumab; fluoropyrimidines (eg, capecitabine or 5-fluorouracil, 5FU); or
temozolomide
- Poorly-differentiated or high-grade pancreatic neuroendocrine tumors
- Prior full field radiotherapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior
to enrollment
- Diagnosis of another malignancy, unless > 3 years earlier and has been disease-free
for > 6 months following the completion of curative intent therapy, specific
eligibility exceptions as follows:
- Curatively-resected non-melanomatous skin cancer
- Curatively-treated cervical carcinoma in situ
- Organ-confined prostate cancer with no evidence of recurrent or progressive disease
based on prostate-specific antigen (PSA) values, if hormonal therapy has been
initiated or a radical prostatectomy has been performed
- Other primary solid tumor curatively treated with no known active disease present and
no treatment administered for > 3 years
- Concurrent use of other investigational agents and patients who have received
investigational drugs ≤ 4 weeks prior to enrollment
- Known hypersensitivity to capecitabine, temozolomide, or any component of the
formulation
- Known deficiency of dihydropyrimidine dehydrogenase Bevacizumab-specific Exclusions
- Inadequately-controlled hypertension (defined as systolic blood pressure >150 mmHg
and/or diastolic blood pressure > 100 mmHg)
- Prior history of hypertensive crisis or hypertensive encephalopathy
- New York Heart Association (NYHA) Grade II or greater congestive heart failure
- History of myocardial infarction or unstable angina within 6 months prior to Day 1
- History of stroke or transient ischemic attack within 6 months prior to Day 1
- Known central nervous system (CNS) metastases
- Significant vascular disease (eg, aortic aneurysm, requiring surgical repair or recent
peripheral arterial thrombosis) within 6 months prior to Day 1
- History of hemoptysis (≥ ½ teaspoon of bright red blood per episode) within 1 month
prior to Day 1
- Evidence of bleeding diathesis or significant coagulopathy (in the absence of
therapeutic anticoagulation)
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 1 or anticipation of need for major surgical procedure during the course
of the study
- Core biopsy or other minor surgical procedure, excluding placement of a vascular
access device, within 7 days prior to Day 1
- History of abdominal fistula or gastrointestinal perforation within 6 months prior to
Day 1
- Serious, non-healing wound, active ulcer, or untreated bone fracture
- Known hypersensitivity to any component of bevacizumab General Medical Exclusions
- Inability to comply with study and/or follow-up procedures
- Current, recent (within 4 weeks of the first infusion of this study), or planned
participation in an experimental drug study
- Pregnant or lactating/breast feeding
- Lack of effective contraception men or women of child-bearing potential
- Uncontrolled systemic fungal, bacterial, viral, or other infection (defined as
exhibiting ongoing signs/symptoms related to the infection and without improvement,
despite appropriate antibiotics or other treatment)
- Known history of HIV, HBV, or HCV
- Current, ongoing treatment with full-dose warfarin. However, patients may be on stable
doses of a low-molecular weight heparin are allowed [eg, (enoxaparin (Lovenox)].
Intervention(s):
biological: bevacizumab
drug: Capecitabine
drug: Temozolomide
Not Recruiting
Contact Information
Stanford University
School of Medicine
300 Pasteur Drive
Stanford,
CA
94305
Cancer Clinical Trials Office
650-498-7061