Pazopanib as Single Agent in Advanced NETs
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|ClinicalTrials.gov Identifier: NCT01280201|
Recruitment Status : Completed
First Posted : January 20, 2011
Results First Posted : March 4, 2019
Last Update Posted : May 29, 2019
The incidence of new diagnosed patients with NET of the digestive tract including carcinoid and pancreatic islet cells tumors ranges from 2 to 10 per 100,000 in the western Countries (Kulke M, Mayer R. N Engl J Med 340:858-868, 1999). Despite of the low incidence, the prevalence of these tumors is high because of their relatively long survival estimated in 35% at 5 years for those patients with well or moderate differentiated tumors (Yao JC, et al. J Clin Oncol. 2008;26:3063-3072). In fact, digestive NETs are the second most prevalent tumors derived from the digestive tract after colorectal carcinoma.
NETs are characterized by abundant vasculature, moreover VEGFR and VEGFR are overexpressed in 60-84% of the carcinoids and pancreatic islet cells NETs (Zhang et al. Cancer 2007;109:1478-1486). Other pro-angiogenic factors like the platelet derived growth factor (PDGFR) have been also involved in NET progression and development (Chaudhry A, et al.Cancer Res 1992;52:1006-12).
Pazopanib is an oral tyrosine kinase inhibitor of the VEGFR, PDGFR and KIT with a dual activity both as an antiangiogenic and also and anti-tumoral agent (Kumar et al. Mol Cancer Ther2007;6:2012-2021, Hurwitz et al. Clin Cancer Res 2009;15:4220-4227). Pazopanib seems to have a better toxicity profile versus the other antiangiogenic tyrosine kinase inhibitors and has already shown activity in several tumor types like renal cell carcinoma (Sternberg et al. J Clin Oncol 2009;27:abst. 5021), soft tissue sarcomas (Sleijfer et al. J Clin Oncol 2009;27:3126-32), hepatocellular carcinoma (Yau et al. J Clin Oncol 2009;27:abst. 3561), colorectal cancer (Brady et al. J Clin Oncol 2009;27:abst.4133), and thyroid cancers (Bible et al. J Clin Oncol 2009;27:abst. 3521).
The Spanish Group for Research in Neuroendocrine Tumors (GETNE) group is an active Member inside of the GENET group and has a large tradition in clinical trials in NETs. The investigators hypothesize that pazopanib may have at least as good activity and better safety profile than other VEGFR inhibitors in progressive advanced or metastatic NET tumors derived from the digestive tract.
|Condition or disease||Intervention/treatment||Phase|
|Advanced/Metastatic Neuroendocrine Tumors||Drug: Pazopanib||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||44 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II, Open Label, Uncontrolled and Multicenter Trial of Pazopanib Given as a Single Agent in Patients With Progressive Advanced/Metastatic Neuroendocrine Tumors (NET): a Search for Activity, Safety, and Predictive Biomarkers|
|Actual Study Start Date :||January 26, 2011|
|Actual Primary Completion Date :||April 2013|
|Actual Study Completion Date :||March 15, 2015|
Single arm of pazopanib 800 mg (2x400mg) given once daily as a single agent.
- Clinical Benefit Rate [ Time Frame: 6 months ]Per Response Evaluation Criteria In Solid Tumor Criteria (RECIST v1.0) for target lesions and assessed by MRI: complete response (CR) considered as dissapereance of all target lesions: partial response (PR), considered as >=30% decrease in the sum of the longest diameter of target lesions, or stable disease (SD) considered as a decrease <30%, after pazopanib was started. Clinical benefit rate (CBR) was defined as the percentage of patients achieving CR, PR or SD.
- Number of Patients Who Had an Event (Disease Progression or Death) [ Time Frame: 3 years ]Per Response Evaluation Criteria In Solid Tumor Criteria (RECIST v1.0) for target lesions and assessed by MRI, considered as the proportion of patietnts whose target lesions have been reported with a >=30% increase in the sum of the longest diameter of target lesions.
- Radiological Objective Complete Response Rate [ Time Frame: 3 years ]Per Response Evaluation Criteria In Solid Tumor Criteria (RECIST v1.0) for target lesions and assessed by MRI, considered as the proportion of patients whose target lessions have dissaperead after treatment.
- Duration of Response (DoR) [ Time Frame: 3 years ]Defined, for the subset of patients with a confirmed CR o PR, as the time from first documented evidence of CR or PR until first documented disease progression or death due to any cause. The DR data will be censored the day after the last evaluation in those patients who did not present an objective tumoral progression and did not died during their participation in the trial. The DR will be assessed only in the subset of patients presenting objective response.
- Safety Assessment Criteria [ Time Frame: 3 years ]Security and tolerance to the study medication will be determined evaluating the type, incidence, severity, timing, seriousness and connections with the treatment of the reported adverse events, physical examinations and laboratory tests. Toxicity will be classified according to NCI-CTCAE v 4.0.
- Predictive Value of Baseline CTC (Count of 0) for Response to Treatma [ Time Frame: 3 years ]Predictive value of the differente biomarkers included in the study was evaluated using multivariate analysis.
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01280201
|Institut Català d'Oncologia L'Hospitalet|
|L'Hospitalet de Llobregat, Barcelona, Spain|
|Hospital Universitari Vall d'Hebron|
|Centro Integral Oncológico Clara Campal|
|Hospital Clínico San Carlos|
|Hospital Universitario 12 de Octubre|
|Hospital Universitario Ramón y Cajal|
|Hospital Universitario Virgen de la Victoria|
|Hospital Universitari Son Espases|
|Palma de Mallorca, Spain|
|Hospital Universitario Virgen del Rocío|
|Hospital Clínico Universitario Lozano Blesa|
|Study Chair:||Enrique Grande Pulido, MD||Grupo Espanol de Tumores Neuroendocrinos|