This randomized phase III trial studies octreotide acetate and recombinant interferon alfa-2b to see how well it works compared to octreotide acetate and bevacizumab in treating patients with high-risk neuroendocrine tumors that have spread to other places in the body (metastatic) or spread from where it started to nearby tissue or lymph nodes (locally advanced). Octreotide acetate and recombinant interferon alfa-2b may interfere with the growth of tumor cells and slow the growth of cancer. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving octreotide acetate together with recombinant interferon alfa-2b is more effective than giving octreotide acetate together with bevacizumab in treating patients with neuroendocrine tumor.
PRIMARY OBJECTIVES: I. To compare central review-based progression-free survival in poor prognosis carcinoid patients treated with either depot octreotide (octreotide acetate) plus bevacizumab, or depot octreotide plus interferon (recombinant interferon alfa-2b). SECONDARY OBJECTIVES: I. To compare overall survival, time to treatment failure and traditionally reported progression-free survival in poor prognosis carcinoid patients treated with either depot octreotide plus bevacizumab, or depot octreotide plus interferon. II. To compare objective response (confirmed and unconfirmed complete response \[CR\] and partial response \[PR\]) in poor prognosis carcinoid patients treated with either depot octreotide plus bevacizumab, or depot octreotide plus interferon. III. To compare the toxicity profile of patients treated with these two regimens. TERTIARY OBJECTIVES: I. To assess the prognostic and predictive value of vascular endothelial growth factor (VEGF) expression in relation to progression-free survival and treatment effect. II. To compare response of 5HIAA, chromogranin A and neuronspecific enolase among patients with elevated levels at baseline between patients treated with octreotide plus interferon versus octreotide plus bevacizumab. III. To assess and compare the prognostic and predictive value of the combination of In-111 pentetreotide somatostatin-receptor scintigraphy (SRS) and computed tomography (CT) vs. CT in relation to progression-free survival (PFS). IV. To assess and compare the prognostic and predictive value of the combination of SRS and CT vs. CT in relation to overall survival (OS) and time to treatment failure (TTF). OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive octreotide acetate intramuscularly (IM) and bevacizumab intravenously (IV) over 30-90 minutes on day 1. ARM II: Patients receive octreotide acetate IM on day 1 and recombinant interferon alfa-2b subcutaneously (SC) on days 1, 3, 5, 8, 10, 12, 15, 17, and 19. Treatment in both arms repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 2-6 months for up to 3 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
427
Given IV
Correlative studies
Given IM
Given SC
Providence Hospital
Mobile, Alabama, United States
Fairbanks Memorial Hospital
Fairbanks, Alaska, United States
Mercy Hospital Fort Smith
Fort Smith, Arkansas, United States
NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
Jonesboro, Arkansas, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Central Review-based Progression-Free Survival
From date of randomization (which is the date of registration) to date of first documentation of progression based on Central Radiological Review of the appropriate CT or MRI scans, or symptomatic deterioration (as defined in Section 10.2e)), or development of new lesions or disease not identified on CT or MRI, or death due to any cause. Patients who have a local assessment of progression based on imaging, but for whom central review does not concur, will be censored at the last Central Radiological Review date, unless subsequent scans or documentation of symptomatic deterioration provides evidence of progression. Patients last known not to have progressed are censored at the date of last contact. Patients with incomplete Central Radiological Review are censored at the date of last Central Radiological Review if patient has not progressed prior to that time.
Time frame: Up to 3 years
Overall Survival
From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
Time frame: Up to 7 years
Time to Treatment Failure
From date of randomization (which is the date of registration) to date of first observation of progressive disease (as defined in Section 10.2d), death due to any cause, symptomatic deterioration (as defined in Section 10.2e), or discontinuation of treatment. This has been calculated using Central-Review based progression events. Patients last known not to have failed treatment are censored at date last known not to have failed. Patients with incomplete Central Radiological Review are censored at the date of last Central Radiological Review if patient has not failed treatment prior to that time.
Time frame: Up to 3 years
Local Progression-Free Survival (Investigator Assessed)
From date of randomization (which is the date of registration) to date of first documentation of progression \[per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as defined in Section 10.2d\] or symptomatic deterioration (as defined in Section 10.2e), or death due to any cause. Patients last known not to have progressed are censored at date of last contact. Progression (Section 10.2d) includes one or more of the following: 20% increase in the sum of the longest diameters of target measurable lesions over smallest sum observed using the same techniques as baseline; unequivocal progression of non-measurable disease in the opinion of the treating physician; appearance of new lesion/site; or death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration (Section 10.2e) is global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.
Time frame: Up to 3 years
Objective Response (Confirmed and Unconfirmed Complete Response and Partial Response)
Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0): Complete Response (CR) is disappearance of all measurable and non-measurable disease, and no new lesions; Partial Response (PR) is greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions, no unequivocal progression of non-measurable disease, and no new lesions. Confirmed response is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.
Time frame: Up to 3 years
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug
Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time frame: Up to 3 years
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