Randomized Phase II Study of Everolimus Alone Versus Everolimus Plus Bevacizumab in Patients With Locally Advanced or Metastatic Pancreatic Neuroendocrine Tumors
Randomized Phase II Study of Everolimus Alone Versus Everolimus Plus Bevacizumab in Patients With Locally Advanced or Metastatic Pancreatic Neuroendocrine Tumors
This randomized phase II trial studies how well everolimus and octreotide acetate with or without bevacizumab works in treating patients with pancreatic neuroendocrine tumors that cannot be removed by surgery and have spread nearby or to other places in the body. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Octreotide acetate may interfere with and slow the growth of tumor cells. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab and everolimus also may stop the growth of pancreatic neuroendocrine tumors by blocking blood flow to the tumor. It is not yet known whether giving everolimus and octreotide acetate together is more effective with or without bevacizumab in treating pancreatic neuroendocrine tumors.
PRIMARY OBJECTIVES:
l. To assess the progression-free survival rate of patients with locally advanced or metastatic pancreatic neuroendocrine tumors treated with everolimus alone or everolimus plus bevacizumab.
SECONDARY OBJECTIVES:
I. To compare progression-free survival (PFS) among treatment arms shown to be efficacious.
II. To estimate the overall tumor response rate in patients with metastatic pancreatic neuroendocrine tumors treated with one of two novel regimens.
III. To estimate the overall biochemical response rate (as measured by plasma chromogranin A levels) in patients with metastatic pancreatic neuroendocrine tumors treated with these regimens.
IV. To assess the toxicity of each regimen in patients with metastatic pancreatic neuroendocrine tumors.
V. To assess the overall survival of patients with pancreatic neuroendocrine tumors treated with these regimens.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive everolimus orally (PO) once daily (QD) on days 1-28 and octreotide acetate intramuscularly (IM) on day 1.
ARM II: Patients receive everolimus and octreotide acetate as in Arm I. Patients also receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15.
In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3-6 months for 3 years.
Inclusion Criteria:
Patients must have histologic documentation of well-differentiated or moderately differentiated neuroendocrine tumor from either a primary or metastatic site
Locally unresectable or metastatic disease
Patients must have either histologic documentation of a pancreatic primary site, or clinical evidence of a pancreatic neuroendocrine primary tumor as determined by the treating physician
Patients must have evidence of disease (measurable or non-measurable) with evidence of progression within the past 12 months
Measurable disease:
Lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 2 cm with conventional techniques or as >= 1 cm with spiral computed tomography (CT) scan
All other lesions, including small lesions (longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan) and truly non-measurable lesions; lesions that are considered non-measurable include the following:
Bone lesions
Leptomeningeal disease
Ascites
Pleural/pericardial effusion
Inflammatory breast disease
Lymphangitis cutis/pulmonis
Abdominal masses that are not confirmed and followed by imaging techniques
Cystic lesions
There is no limit on the number of prior treatment regimens
Any prior treatment (with the exception of octreotide) must be completed at least 4 weeks prior to initiation of treatment
There is no limit on the prior number of procedures
Patients receiving octreotide at the time of study entry may continue at the same dose level for the duration of the study
Patients not receiving octreotide will initiate treatment according to study guidelines
Prior progression on somatostatin analogs or a negative octreotide scan does not exclude patient participation in this study
Patients must have completed any minor surgery >= 2 weeks prior to start of treatment
Patients must have fully recovered from the procedure
Insertion of a vascular access device is not considered major or minor surgery
If urine protein creatinine (UPC) ratio is > 1 on urinalysis, then 24-hour urine collection for protein must be obtained and level must be < 1,000 mg for patient enrollment
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