Status:
COMPLETED
Capecitabine, Temozolomide, and Bevacizumab for Metastatic or Unresectable Pancreatic Neuroendocrine Tumors
Lead Sponsor:
Shaheen Shagufta
Collaborating Sponsors:
National Cancer Institute (NCI)
Conditions:
Gastrinoma
Glucagonoma
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
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.
Detailed Description
PRIMARY OBJECTIVES: * Estimate if the combination of capecitabine and temozolomide with bevacizumab for metastatic or unresectable neuroendocrine tumors will improve response rate (RR) by 62% over hi...
Eligibility Criteria
Inclusion
- 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 \[eg, (enoxaparin (Lovenox)\].
Exclusion
Key Trial Info
Start Date :
December 1 2012
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
December 31 2019
Estimated Enrollment :
20 Patients enrolled
Trial Details
Trial ID
NCT01525082
Start Date
December 1 2012
End Date
December 31 2019
Last Update
February 6 2024
Active Locations (1)
Enter a location and click search to find clinical trials sorted by distance.
1
Stanford University Medical Center
Stanford, California, United States, 94305