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

Phase 3

Terminated

• Conditions: Carcinoma, Islet Cell; Carcinoma, Pancreas
• Interventions: Drug: Placebo; Drug: sunitinib malate

• Registration Number: NCT00428597
• Lead Sponsor: Pfizer

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.

Study Timeline

• Study First Submitted: 2007-01-29
• Study First Submitted QC: 2007-01-29
• Study First Posted: 2007-01-30
• Study Start: 2007-06
• Primary Completion: 2009-04
• Study Completion: 2009-04
• Results First Submitted: 2010-04-15
• Status Verified: 2010-09
• Results First Submitted QC: 2010-09-16
• Last Update Submitted: 2010-09-16
• Results First Posted: 2010-10-11
• Last Update Posted: 2010-10-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 171

Inclusion Criteria

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
B	Placebo	-
A	sunitinib malate	-

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	From time of randomization through Day 1 of Week 5, Week 9, and then every 8 weeks thereafter until disease progression or death	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.

Secondary Outcome Measures

Name	Time	Method
Number of Subjects With Objective Response	From time of randomization through Day 1 of Week 5, 9, and every 8 weeks thereafter	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.
Duration of Response (DR)	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 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.
Time-to-Tumor Response (TTR)	From time of randomization through Day 1 of Week 5, 9, and every 8 weeks thereafter	Time from randomization to the first documentation of objective tumor response (CR or PR) that was subsequently confirmed.
Overall Survival (OS)	From start of study treatment up to 22 months	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.
European Organization for Research and Treatment of Cancer Quality of LifeQuestionnaire (EORTC QLQ-C30) - Global Quality of Life (QoL) Subscale	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal	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.
EORTC QLQ-C30 - Cognitive Functioning Subscale	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal	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.
EORTC QLQ-C30 - Emotional Functioning Subscale	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal	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.
EORTC QLQ-C30 - Physical Functioning Subscale	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal	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.
EORTC QLQ-C30 - Role Functioning Subscale	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal	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.
EORTC QLQ-C30 - Social Functioning Subscale	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal	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.
EORTC QLQ-C30 - Appetite Loss Subscale	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal	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.
EORTC QLQ-C30 - Constipation Subscale	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal	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.
EORTC QLQ-C30 - Diarrhea Subscale	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal	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.
EORTC QLQ-C30 - Dyspnea Subscale	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal	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.
EORTC QLQ-C30 - Fatigue Subscale	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal	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.
EORTC QLQ-C30 - Financial Difficulties Subscale	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal	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.
EORTC QLQ-C30 - Insomnia Subscale	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal	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.
EORTC QLQ-C30 - Nausea and Vomiting Subscale	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal	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.
EORTC QLQ-C30 - Pain Subscale	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal	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.

Trial Locations

Locations (1)

Pfizer Investigational Site; 🇬🇧 Manchester, United Kingdom