Sunitinib may provide an opportunity for a novel therapeutic strategy for the treatment of subjects with neuroendocrine tumors.
With the exception of surgery for localized disease, there is presently a lack of available therapies with proven survival benefit for patients with neuroendocrine tumors (NET). Available treatment options for unresectable disease include the use of somatostatin analogs, which may relieve symptoms related to hormonal hypersecretion. The efficacy of cytotoxic chemotherapy in patients with metastatic carcinoid tumors is also limited. Combinations of either streptozocin and cyclophosphamide, or streptozocin and 5-fluorouracil, appear to be inactive, and both regimens are associated with substantial toxicity. Receptor tyrosine kinases (RTKs) are implicated in deregulated/ autocrine proliferation and survival of solid and hematologic cancer cells. Sunitinib malate is an orally administered small molecule that inhibits the tyrosine kinase enzymatic activities of the receptors for VEGF and PDGF, and also blocks signalling through the KIT, FLT3 and RET pathways. Therefore, sunitinib malate may provide an opportunity for a novel therapeutic strategy for the treatment of subjects with NET.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
44
Lanreotide at the dose of 120 mg will be injected every 28 days as the reference treatment to control the carcinoid syndrome in both arms.
Sunitinib 37.5 mg daily
Cliniques Universitaires Saint Luc
Brussels, Belgium
Institut Jules Bordet
Brussels, Belgium
ULB Erasme
Brussels, Belgium
Progression free survival (PFS)
To evaluate the efficacy of the combination of sunitinib malate with lanreotide acetate and of placebo with lanreotide acetate regarding progression-free-survival (PFS) as assessed by the investigator, in patients suffering from progressive, advanced/metastatic midgut carcinoid tumors.
Time frame: time from date of randomization to first progression of disease (PD) or death for any reason in the absence of documented PD, assessed up to 3 years after the beginning of the study
Overall survival (OS)
To evaluate overall survival (OS) in sunitinib- and placebo-treated subjects.
Time frame: time from date of randomization to date of death, assessed up to 3 years after the beginning of the study
Objective response (OR)
To evaluate objective response (OR) rate in sunitinib- and placebo-treated subjects.
Time frame: from randomization until disease progression, assessed up to 3 years after the beginning of the study
Duration of response (DR)
To evaluate duration of response (DR) in sunitinib- and placebo-treated subjects in subjects achieving a response.
Time frame: time from CR or PR to objective tumor progression or to death due to any cause, whichever occurs first, assessed up to 3 years after the beginning of the study
Time to tumor response (TTR)
To assess time to tumor response (TTR) for sunitinib- and placebo-treated subjects.
Time frame: time from date of randomization to first documentation of objective tumor response that is subsequently confirmed.assessed up to 3 years after the beginning of the study
Biological responses
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UZ Antwerpen
Edegem, Belgium
UZ Gent
Ghent, Belgium
UZ Leuven
Leuven, Belgium
Hôpital Saint André
Bordeaux, France
Hôpital Beaujon
Clichy, France
Hôpital Henri Mondor
Créteil, France
Hopital Saint Vincent de Paul
Lille, France
...and 10 more locations
To evaluate the best biological responses as assessed using serum chromogranin A and urine 5HIAA for sunitinib- and placebo-treated subjects.
Time frame: from baseline to end of treatment, assessed up to 3 years after the beginning of the study
Safety
To assess safety and tolerability of sunitinib in the study population.
Time frame: from visit 1 to 1 month after last study drug administration, assessed up to 3 years after the beginning of the study
Quality of life
To assess Health related Quality of life (EORTC QLQ C-30).
Time frame: From screening to 1 month after last study drug administration, assessed up to 3 years after the beginning of the study