S0518 - Phase III Prospective Randomized Comparison of Depot Octreotide Plus Interferon Alpha Versus Depot Octreotide Plus Bevacizumab (NSC #704865) in Advanced, Poor Prognosis Carcinoid Patients
Description
S518 - Phase III Prospective Randomized Comparison of Depot Octreotide Plus Interferon Alpha Versus Depot Octreotide Plus Bevacizumab (NSC #704865) in Advanced, Poor Prognosis Carcinoid Patients
To compare central review-based progression-free survival in poor prognosis carcinoid patients treated with either depot octreotide plus bevacizumab, or depot octreotide plus interferon.
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.
To compare objective response (confirmed and unconfirmed CR and PR) in poor prognosis carcinoid patients treated with either depot octreotide plus bevacizumab, or depot octreotide plus interferon.
To compare the toxicity profile of patients treated with these two regimens.
To assess the prognostic and predictive value of VEGF expression in relation to progression-free survival and treatment effect.
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.
To assess and compare the prognostic and predictive value of the combination of In-111 pentetreotide somatostatin-receptor scintigraphy (SRS) and CT vs. CT in relation to progression-free survival (PFS).
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).
Study/Treatment
Carcinoid Cancer Trial
Inclusion/Notes
Eligibility Criteria:
Patient must have unresectable metastatic or locally advanced, low- or intermediategrade neuroendocrine carcinoma.
Patient must have high risk disease as defined by at least one of the following: Progressive disease, refractory carcinoid syndrome while receiving octreotide (defined by > 2 flushing episodes/day or > 4 bowel movements/day), atypical histology and more than 6 lesions, metastatic colorectal carcinoid (patients with metastatic cecal or appendiceal
carcinoid tumor are not eligible unless the tumors fit into one of the other high-risk categories), metastatic gastric carcinoid.
Patient must have measurable disease. CT or MRI must have been completed within 28 days prior to registration.
Patient may have had up to one prior regimen of cytotoxic chemotherapy. At least 28 days must have elapsed since completion of prior therapy, and patient must have recovered from all effects.
Patient may have had prior hepatic artery embolization. At least 28 days must have elapsed since embolization and there must be residual measurable disease. Chemoembolization will be considered as one prior chemotherapy regimen.
Patient must not have received prior interferon, bevacizumab, or any other therapy targeting VEGF or VEGF receptors (i.e., SU11248, PTK/ZK, BAY 43-9006, GW786034).
Patient may have received prior therapy targeting c-kit, abl, PDGFR, mTOR, and somatostatin receptors (not counted toward prior cytotoxic chemotherapy).
Prior radiation is allowed. There must be measurable disease. If prior therapies include peptide receptor radiotherapy, the target lesion(s) must have shown disease progression. At least 28 days must have elapsed since completion of prior therapy, and patient must have recovered from all effects.
Patients must have recovered from any prior surgery. At least 21 days must have elapsed since any prior octreotide LAR depot treatment.
Patient must have a Zubrod performance status of 0-2
Patient must have ANC > 1,500/mcl, hemoglobin > 8 g/dl, and platelets > 100,000/mcl
Patient must have adequate liver function as evidenced by serum bilirubin < 1.5 x institutional upper limit of normal (IULN) and either SGOT or SGPT = 2.5 x IULN.
Patient must have adequate renal function as evidenced by serum creatinine < 1.5 mg/dL
Urine protein must be screened by urine analysis for Urine Protein Creatinine (UPC) ratio. For UPC ratio > 0.5, 24-hour urine protein must be obtained and the level must be < 1,000 mg for patient enrollment.
Patients not on anticoagulation must have PT and PTT = 1.1 x lULN obtained within 28 days prior to registration. Patients on full-dose anticoagulation (warfarin or low molecular weight heparin) are eligible provided that both of the following criteria are met: The patient has an in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin. The patient has no active bleeding or pathological condition that carries a high risk of bleeding such as varices.
Patient must not have history or evidence of clinically significant peripheral vascular disease such as non-healing peripheral ulcers or claudication.
Patient must not have a history of primary brain tumor or metastatic cancer to the brain.
Patient must not have a history of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 28 days.
Patient must not have history within the past 5 years or presence of bleeding diathesis or coagulopathy that results in spontaneous bleeding (in the absence of trauma) requiring pRBC transfusion.
Patient must not have a serious (requiring active medical therapy with medication or medical device under the supervision of a physician) non-healing wound, ulcer, or bone fracture.
Patient must not have recent history (within 6 months prior to registration) of these arterial thromboembolic events: transient ischemic attack, cerebrovascular accident, unstable angina, myocardial infarction, or New York Heart Association Grade II or higher congestive heart failure.
Patients with a history of hypertension must be well-controlled (blood pressure < 150/90), on a stable regimen of antihypertensive therapy.
Patient must not have hemoglobinopathies (e.g., Thalassemia) or any other cause of hemolytic anemia.
Patient must not plan to use any other concurrent chemotherapy, immunotherapy, hepatic artery embolization, hepatic artery chemoembolization, radiofrequency ablation, other tumor ablative procedure or radiotherapy while on protocol treatment.
Patient must not be pregnant or nursing
No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer, or any other cancer from which the patient has been disease free for five years.
All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
Start Date
09/21/2010
Principal Name
O. George Negrea
Contact Name
Nancy N. and J.C. Lewis Cancer & Research Pavilion
Fax
(912) 819-5705
Phone
(912) 819-5704
Nancy N. and J.C. Lewis Cancer & Research Pavilion225 Candler Drive, Savannah, Georgia 31405
