Clinical trial NCT00428597: A Study Of Sunitinib Compared To Placebo For Patients With Advanced Pancreatic Islet Cell Tumors
Official title: A Phase III Randomized, Double-Blind Study Of Sunitinib (SU011248, SUTENT) Versus Placebo In Patients With Progressive Advanced/Metastatic Well-Differentiated Pancreatic Islet Cell Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Carcinoma, Islet Cell
Carcinoma, Pancreas
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2007-01-30
Enrollment: 171
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study randomized patients with advanced pancreatic islet cell tumors to receive either sunitinib or placebo. Patients who were randomized to sunitinib received 37.5 mg of sunitinib daily, those randomized to placebo received a tablet that looked similar but had no active drug. Neither the patient or the doctor knew whether the patient was receiving sunitinib or placebo. Patients were followed to determine the status and size of their tumors, survival, quality of life and safety of the drug.

The study was designed to detect a 50% improvement in median PFS\[Progression Free Survival\] with 90% power and was to enroll 340 subjects. An interim analysis was planned when 130 events had occurred, and the final analysis was to be conducted when 260 events had occurred.

Study A6181111 was stopped early during the enrollment period because of a clear and clinically meaningful improvement in efficacy for the sunitinib treatment arm as recommended by the DMC \[Data Monitoring Committee\]. The actual number of subjects enrolled was 171 and the actual number of PFS events recorded was 81 PFS events. The decision to terminate the study was not based on safety concerns related to sunitinib administration.

Detailed description: The study was terminated on 11 March 2009 because the independent Data Monitoring Committee determined that the study had met its primary endpoint in demonstrating improvement in progression-free survival. The decision to terminate the trial was not based on safety concerns related to sunitinib administration.

Eligibility criteria: Inclusion Criteria:

* Well-differentiated advanced/metastatic pancreatic islet cell tumor
* Tumor has shown progression within the past year.

Exclusion Criteria:

* Current treatment with any chemotherapy, chemoembolization therapy, immunotherapy, or investigational anticancer agent other than somatostatin analogues
* Prior treatment with any tyrosine kinase inhibitors or anti-VEGF\[Vascular endothelial growth factor\] angiogenic inhibitors.
* Prior treatment with non-VEGF-targeted angiogenic inhibitors is permitted

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From time of randomization through Day 1 of Week 5, Week 9, and then every 8 weeks thereafter until disease progression or death
Secondary outcomes:
measure: Number of Subjects With Objective Response
timeFrame: From time of randomization through Day 1 of Week 5, 9, and every 8 weeks thereafter
measure: Duration of Response (DR)
timeFrame: From start of treatment through Day 1 of Week 5, 9, and every 8 weeks thereafter until disease progression or death due to any cause
measure: Time-to-Tumor Response (TTR)
timeFrame: From time of randomization through Day 1 of Week 5, 9, and every 8 weeks thereafter
measure: Overall Survival (OS)
timeFrame: From start of study treatment up to 22 months
measure: European Organization for Research and Treatment of Cancer Quality of LifeQuestionnaire (EORTC QLQ-C30) - Global Quality of Life (QoL) Subscale
timeFrame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
measure: EORTC QLQ-C30 - Cognitive Functioning Subscale
timeFrame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
measure: EORTC QLQ-C30 - Emotional Functioning Subscale
timeFrame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
measure: EORTC QLQ-C30 - Physical Functioning Subscale
timeFrame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
measure: EORTC QLQ-C30 - Role Functioning Subscale
timeFrame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
measure: EORTC QLQ-C30 - Social Functioning Subscale
timeFrame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
measure: EORTC QLQ-C30 - Appetite Loss Subscale
timeFrame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
measure: EORTC QLQ-C30 - Constipation Subscale
timeFrame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
measure: EORTC QLQ-C30 - Diarrhea Subscale
timeFrame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
measure: EORTC QLQ-C30 - Dyspnea Subscale
timeFrame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
measure: EORTC QLQ-C30 - Fatigue Subscale
timeFrame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
measure: EORTC QLQ-C30 - Financial Difficulties Subscale
timeFrame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
measure: EORTC QLQ-C30 - Insomnia Subscale
timeFrame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
measure: EORTC QLQ-C30 - Nausea and Vomiting Subscale
timeFrame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
measure: EORTC QLQ-C30 - Pain Subscale
timeFrame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Pfizer Investigational Site
state: Colorado
city: Iowa City
country: United States
facility: Pfizer Investigational Site
state: Iowa
city: Worcester
country: United States
facility: Pfizer Investigational Site
state: Massachusetts
city: Worcester
country: United States
facility: Pfizer Investigational Site
state: Massachusetts
city: Creve Coeur
country: United States
facility: Pfizer Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: Pfizer Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: Pfizer Investigational Site
state: Missouri
city: St. Peters
country: United States
facility: Pfizer Investigational Site
state: Missouri
city: Austin
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Austin
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Austin
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Austin
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Georgetown
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Norfolk
country: United States
facility: Pfizer Investigational Site
state: Virginia
city: Perth
country: Australia
facility: Pfizer Investigational Site
state: Western Australia
city: Bruxelles
country: Belgium
facility: Pfizer Investigational Site
city: Bruxelles
country: Belgium
facility: Pfizer Investigational Site
city: Leuven
country: Belgium
facility: Pfizer Investigational Site
city: Vancouver
country: Canada
facility: Pfizer Investigational Site
state: British Columbia
city: Halifax
country: Canada
facility: Pfizer Investigational Site
state: Nova Scotia
city: Halifax
country: Canada
facility: Pfizer Investigational Site
state: Nova Scotia
city: Halifax
country: Canada
facility: Pfizer Investigational Site
state: Nova Scotia
city: Toronto
country: Canada
facility: Pfizer Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: Pfizer Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: Pfizer Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: Pfizer Investigational Site
state: Quebec
city: Paris
country: France
facility: Pfizer Investigational Site
state: Be1 05677
city: Paris
country: France
facility: Pfizer Investigational Site
state: Cedex
city: Bordeaux
country: France
facility: Pfizer Investigational Site
city: Clichy Cedex
country: France
facility: Pfizer Investigational Site
city: Lyon
country: France
facility: Pfizer Investigational Site
city: Marseille
country: France
facility: Pfizer Investigational Site
city: Rennes Cedex
country: France
facility: Pfizer Investigational Site
city: Bad Berka
country: Germany
facility: Pfizer Investigational Site
city: Berlin
country: Germany
facility: Pfizer Investigational Site
city: Heidelberg
country: Germany
facility: Pfizer Investigational Site
city: Luebeck
country: Germany
facility: Pfizer Investigational Site
city: Marburg
country: Germany
facility: Pfizer Investigational Site
city: Ulm
country: Germany
facility: Pfizer Investigational Site
city: Cremona
country: Italy
facility: Pfizer Investigational Site
city: Milano
country: Italy
facility: Pfizer Investigational Site
city: Rozzano (MI)
country: Italy
facility: Pfizer Investigational Site
city: Seoul
country: Korea, Republic of
facility: Pfizer Investigational Site
city: Seoul
country: Korea, Republic of
facility: Pfizer Investigational Site
city: Barcelona
country: Spain
facility: Pfizer Investigational Site
city: Barcelona
country: Spain
facility: Pfizer Investigational Site
city: Madrid
country: Spain
facility: Pfizer Investigational Site
city: Madrid
country: Spain
facility: Pfizer Investigational Site
city: Madrid
country: Spain
facility: Pfizer Investigational Site
city: Kwei-Shan
country: Taiwan
facility: Pfizer Investigational Site
state: Taoyuan
city: Taipei
country: Taiwan
facility: Pfizer Investigational Site
city: Leeds
country: United Kingdom
facility: Pfizer Investigational Site
city: Liverpool
country: United Kingdom
facility: Pfizer Investigational Site
city: Manchester
country: United Kingdom
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Fazio N, Kulke M, Rosbrook B, Fernandez K, Raymond E. Updated Efficacy and Safety Outcomes for Patients with Well-Differentiated Pancreatic Neuroendocrine Tumors Treated with Sunitinib. Target Oncol. 2021 Jan;16(1):27-35. doi: 10.1007/s11523-020-00784-0. Epub 2021 Jan 7.
citation: Lamarca A, Barriuso J, Kulke M, Borbath I, Lenz HJ, Raoul JL, Meropol NJ, Lombard-Bohas C, Posey J, Faivre S, Raymond E, Valle JW. Determination of an optimal response cut-off able to predict progression-free survival in patients with well-differentiated advanced pancreatic neuroendocrine tumours treated with sunitinib: an alternative to the current RECIST-defined response. Br J Cancer. 2018 Jan;118(2):181-188. doi: 10.1038/bjc.2017.402. Epub 2017 Nov 21.
citation: Vinik A, Bottomley A, Korytowsky B, Bang YJ, Raoul JL, Valle JW, Metrakos P, Horsch D, Mundayat R, Reisman A, Wang Z, Chao RC, Raymond E. Patient-Reported Outcomes and Quality of Life with Sunitinib Versus Placebo for Pancreatic Neuroendocrine Tumors: Results From an International Phase III Trial. Target Oncol. 2016 Dec;11(6):815-824. doi: 10.1007/s11523-016-0462-5.
citation: Faivre S, Niccoli P, Castellano D, Valle JW, Hammel P, Raoul JL, Vinik A, Van Cutsem E, Bang YJ, Lee SH, Borbath I, Lombard-Bohas C, Metrakos P, Smith D, Chen JS, Ruszniewski P, Seitz JF, Patyna S, Lu DR, Ishak KJ, Raymond E. Sunitinib in pancreatic neuroendocrine tumors: updated progression-free survival and final overall survival from a phase III randomized study. Ann Oncol. 2017 Feb 1;28(2):339-343. doi: 10.1093/annonc/mdw561.
citation: Raymond E, Dahan L, Raoul JL, Bang YJ, Borbath I, Lombard-Bohas C, Valle J, Metrakos P, Smith D, Vinik A, Chen JS, Horsch D, Hammel P, Wiedenmann B, Van Cutsem E, Patyna S, Lu DR, Blanckmeister C, Chao R, Ruszniewski P. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011 Feb 10;364(6):501-13. doi: 10.1056/NEJMoa1003825.