A Study Of Sunitinib Compared To Placebo For Patients With Advanced Pancreatic Islet Cell Tumors

Study Overview

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.

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.

Carcinoma, Islet Cell
Carcinoma, Pancreas

DRUG: sunitinib malate
DRUG: Placebo

A6181111

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2007-01-29	Results First Submitted 2010-04-15	Last Update Submitted that met QC Criteria 2010-09-16
First Submitted that Met QC Criteria 2007-01-29	Results First Submitted that Met QC Criteria 2010-09-16	Last Update Posted (ESTIMATED) 2010-10-11
First Posted (ESTIMATED) 2007-01-30	Results First Posted 2010-10-11	Last Verified 2010-09

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
Double

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: A	DRUG: sunitinib malate * sunitinib malate oral starting dose 37.5 mg daily (continuous dosing). * Dose may be decreased to 25 mg daily in case of adverse events. * It may be increased to 50 mg daily if no response is seen after 8 weeks on treatment. * Dosing to continue until u
PLACEBO_COMPARATOR: B	DRUG: Placebo Placebo to match sunitinib taken daily (oral) on the same schedule as active agent below.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: A

DRUG: sunitinib malate

* sunitinib malate oral starting dose 37.5 mg daily (continuous dosing). * Dose may be decreased to 25 mg daily in case of adverse events. * It may be increased to 50 mg daily if no response is seen after 8 weeks on treatment. * Dosing to continue until u

PLACEBO_COMPARATOR: B

DRUG: Placebo

Placebo to match sunitinib taken daily (oral) on the same schedule as active agent below.

Primary Outcome Measures	Measure Description	Time Frame
Progression Free Survival (PFS)	Time from randomization to first progression of disease (PD) or death for any reason in the absence of documented PD. PFS was calculated as (first event date minus first randomization date +1) divided by 30.4.	From time of randomization through Day 1 of Week 5, Week 9, and then every 8 weeks thereafter until disease progression or death

Secondary Outcome Measures	Measure Description	Time Frame
Number of Subjects With Objective Response	Objective response = subjects with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) for at least 4 weeks, confirmed by repeat tumor assessments. A CR was defined as the disappearance of all target lesions. A PR was defined as a > = 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.	From time of randomization through Day 1 of Week 5, 9, and every 8 weeks thereafter
Duration of Response (DR)	Time in months from the first documentation of objective tumor response to objective tumor progression or death due to any cause. DR was calculated as (the date of the first documentation of objective tumor progression or death due to any cause minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.4.	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
Time-to-Tumor Response (TTR)	Time from randomization to the first documentation of objective tumor response (CR or PR) that was subsequently confirmed.	From time of randomization through Day 1 of Week 5, 9, and every 8 weeks thereafter
Overall Survival (OS)	Time in months from time of randomization to date of death due to any cause. The median number of months is provided; however, the study was terminated early. OS data was not mature by the time of analysis. Median OS time cannot be accurately estimated by Kaplan-Meier method for either treatment arm.	From start of study treatment up to 22 months
European Organization for Research and Treatment of Cancer Quality of LifeQuestionnaire (EORTC QLQ-C30) - Global Quality of Life (QoL) Subscale	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
EORTC QLQ-C30 - Cognitive Functioning Subscale	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
EORTC QLQ-C30 - Emotional Functioning Subscale	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
EORTC QLQ-C30 - Physical Functioning Subscale	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
EORTC QLQ-C30 - Role Functioning Subscale	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
EORTC QLQ-C30 - Social Functioning Subscale	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
EORTC QLQ-C30 - Appetite Loss Subscale	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
EORTC QLQ-C30 - Constipation Subscale	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
EORTC QLQ-C30 - Diarrhea Subscale	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
EORTC QLQ-C30 - Dyspnea Subscale	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
EORTC QLQ-C30 - Fatigue Subscale	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
EORTC QLQ-C30 - Financial Difficulties Subscale	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
EORTC QLQ-C30 - Insomnia Subscale	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
EORTC QLQ-C30 - Nausea and Vomiting Subscale	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal
EORTC QLQ-C30 - Pain Subscale	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Pfizer CT.gov Call Center, Pfizer

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.
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.
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.
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.
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.

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