A Study Of Sunitinib Compared To Placebo For Patients With Advanced Pancreatic Islet Cell Tumors - Full Text View

Sponsor:	Pfizer
Information provided by:	Pfizer
ClinicalTrials.gov Identifier:	NCT00428597

Purpose

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.

Condition	Intervention	Phase
Carcinoma, Islet Cell Carcinoma, Pancreas	Drug: sunitinib malate Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Nausea and Vomiting

Drug Information available for: Sunitinib malate Sunitinib Malic acid

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:

Progression Free Survival (PFS) [ Time Frame: From time of randomization through Day 1 of Week 5, Week 9, and then every 8 weeks thereafter until disease progression or death ] [ Designated as safety issue: No ]
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:

Number of Subjects With Objective Response [ Time Frame: From time of randomization through Day 1 of Week 5, 9, and every 8 weeks thereafter ] [ Designated as safety issue: No ]
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) [ Time Frame: 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 ] [ Designated as safety issue: No ]
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) [ Time Frame: From time of randomization through Day 1 of Week 5, 9, and every 8 weeks thereafter ] [ Designated as safety issue: No ]
Time from randomization to the first documentation of objective tumor response (CR or PR) that was subsequently confirmed.
Overall Survival (OS) [ Time Frame: From start of study treatment up to 22 months ] [ Designated as safety issue: No ]
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 [ Time Frame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal ] [ Designated as safety issue: No ]
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 [ Time Frame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal ] [ Designated as safety issue: No ]
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 [ Time Frame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal ] [ Designated as safety issue: No ]
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 [ Time Frame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal ] [ Designated as safety issue: No ]
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 [ Time Frame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal ] [ Designated as safety issue: No ]
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 [ Time Frame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal ] [ Designated as safety issue: No ]
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 [ Time Frame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal ] [ Designated as safety issue: No ]
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 [ Time Frame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal ] [ Designated as safety issue: No ]
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 [ Time Frame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal ] [ Designated as safety issue: No ]
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 [ Time Frame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal ] [ Designated as safety issue: No ]
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 [ Time Frame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal ] [ Designated as safety issue: No ]
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 [ Time Frame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal ] [ Designated as safety issue: No ]
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 [ Time Frame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal ] [ Designated as safety issue: No ]
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 [ Time Frame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal ] [ Designated as safety issue: No ]
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 [ Time Frame: Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal ] [ Designated as safety issue: No ]
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.

Enrollment:	171
Study Start Date:	June 2007
Study Completion Date:	April 2009
Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 unacceptable toxicity, progression of disease, death, or study termination.
Placebo Comparator: B	Drug: Placebo Placebo to match sunitinib taken daily (oral) on the same schedule as active agent below.

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.

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Responsible Party:	Director, Clinical Trial Disclosure Group, Pfizer Inc
ClinicalTrials.gov Identifier:	NCT00428597 History of Changes
Other Study ID Numbers:	A6181111
Study First Received:	January 29, 2007
Results First Received:	April 15, 2010
Last Updated:	September 16, 2010
Health Authority:	United States: Food and Drug Administration