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A Study Of The Efficacy And Safety Of Sunitinib In Patients With Advanced Well-Differentiated Pancreatic Neuroendocrine Tumors

Primary Purpose

Well-differentiated Pancreatic Neuroendocrine Tumor

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
sunitinib
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Well-differentiated Pancreatic Neuroendocrine Tumor focused on measuring neuroendocrine tumors, adenoma islet cells, carcinoma islet cells, pancreatic neoplasms, angiogenesis inhibitors, sunitinib, neoplasms, carcinoma, adenoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically or cytologically proven diagnosis of well-differentiated pancreatic neuroendocrine tumor (according to World Health Organization [WHO 2000] classification).
  • Disease progression within 12 months prior to study enrollment.
  • Disease that is not amenable to surgery, radiation, or combined modality therapy with curative intent.

Exclusion Criteria:

  • Patients with poorly differentiated pancreatic neuroendocrine tumors (according to WHO 2000 classification).
  • Prior treatment with any tyrosine kinase inhibitors, anti vascular endothelial growth factor (VEGF) angiogenesis inhibitors, non VEGF targeted angiogenesis inhibitors, or mammalian target of rapamycin (mTOR) inhibitors.

Sites / Locations

  • Univeristy of California
  • Columbia University Medical Center
  • Barwon Health - University Hospital Geelong
  • Cliniques Universitaires Saint-Luc, Gastroenterologie
  • China-Japan Friendship Hospital
  • 307 Hospital of PLA
  • Beijing Cancer Hospital
  • Nanjing Bayi Hospital
  • West China Hospital of Sichuan University
  • Fudan University Shanghai Cancer Center
  • Zhongshan Hospital Fudan University
  • Masarykuv onkologicky ustav
  • Fakultni poliklinika
  • Vseobecna Fakultni Nemocnice v Praze
  • Hôpital Beaujon
  • Semmelweis Egyetem/II. Sz. Belgyogyaszati Klinika
  • Tata Memorial Hospital
  • IEO Istituto Europeo di Oncologia, IRCCS
  • Kyushu University Hospital
  • National Cancer Center Hospital
  • Oslo Universitetssykehus HF, Rikshospitalet
  • Centrul de Oncologie Sf. Nectarie
  • Institutul Clinic Fundeni, Centrul de Gastroenterologie si Hepatologie
  • Narodny Onkologicky ustav
  • Wits Clinical Research
  • Hospital Universitario Madrid Sanchinarro - Centro Integral Oncológico Clara Campal (CIOCC)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

sunitinib

Arm Description

Outcomes

Primary Outcome Measures

Progression-Free Survival (PFS): Investigator Assessment
Investigator assessed PFS was defined as the time (in months) from the date of enrollment in study to the date of first documented objective tumor progression or death (due to any cause), whichever occurs first. PFS calculated as (first event date minus date of enrollment plus 1)/30.4. If progression or death was not observed, the participant was censored at the date of the participant's last progression-free tumor assessment prior to the study cut-off date. Progression as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 criteria was defined as: greater than or equal to (>=) 20 percent increase in sum of longest diameter (LD) of target lesions taking as a reference the smallest sum of the LD recorded since the treatment started, or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions. The analysis was performed by Kaplan-Meier method.

Secondary Outcome Measures

Progression-Free Survival (PFS): Independent Radiological Review (IRR) Assessment
IRR assessed PFS was defined as the time (in months) from the date of enrollment in study until the date of first documented objective tumor progression or death (due to any cause), whichever occurs first. PFS calculated as (first event date minus date of enrollment plus 1)/30.4. If progression or death was not observed, the participant was censored at the date of the participant's last progression-free tumor assessment prior to the study cut-off date. Progression as per RECIST 1.0 criteria was defined as: >=20 percent increase in sum of LD of target lesions taking as a reference the smallest sum of the LD recorded since the treatment started, or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions. The analysis was performed by Kaplan-Meier method.
Time to Tumor Progression (TTP): Investigator Assessment
Investigator assessed TTP was defined as the time (in months) from the date of enrollment in study until the date of first documentation of objective tumor progression. TTP calculated as (first event date minus date of enrollment plus 1)/30.4. Progression as per RECIST 1.0 was defined as >=20 percent increase in sum of LD of target lesions taking as a reference the smallest sum of the LD recorded since the treatment started, or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions. The analysis was performed by Kaplan-Meier method.
Overall Survival (OS)
OS was defined as the time (in months) from date of enrollment in study to the date of death due to any cause. If death was not observed, the participant was censored at the earliest of the last date the participant was known to be alive or the end of study. The analysis was performed by Kaplan-Meier method.
Percentage of Participants With Objective Response (OR): Investigator Assessment
Investigator assessed OR in participants was defined as having a complete response (CR) or partial response (PR) according to RECIST 1.0 and sustained for at least 4 weeks. CR was defined as disappearance of all target and non-target lesions. PR was defined as >=30 percent decrease in the sum of the LD of the target lesions taking as a reference the baseline sum LD. Percentage of participants with investigator assessed OR were reported.
Duration of Response (DOR): Investigator Assessment
Investigator assessed DOR was defined as the time (in months) from the date of first documented objective tumor response (CR or PR), that was subsequently confirmed, to the first documented objective tumor progression or death due to any cause, whichever occurred first. According to RECIST 1.0, CR was defined as disappearance of all target and non-target lesions. PR was defined as >=30 percent decrease in the sum of the LD of the target lesions taking as a reference the baseline sum LD. Progression as per RECIST version 1.0 was defined as >=20 percent increase in sum of LD of target lesions taking as a reference the smallest sum of the LD recorded since the treatment started, or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions.
Time to Tumor Response (TTR): Investigator Assessment
Investigator assessed TTR was defined as the time (in months) from date of enrollment in study until date of first documentation of objective tumor response (CR or PR) that was subsequently confirmed. TTR was calculated as (first response date minus the date of enrollment plus 1) divided by 30.4. As per RECIST 1.0, CR was defined as disappearance of all target and non-target lesions and PR was defined as >=30 percent decrease in the sum of the LD of the target lesions taking as a reference the baseline sum LD.
Percentage of Participants With Objective Response (OR): Independent Radiological Review (IRR) Assessment
IRR assessed OR in participants was defined as having a CR or PR according to Choi criteria and sustained for at least 4 weeks. According to Choi criteria, CR was defined as disappearance of all target and non-target lesions and no new lesions. PR was defined as a decrease of >=10 percent in tumor size or a decrease in tumor density (HU) of 15 percent or more on Computed tomography (CT) with no new lesions and no obvious progression of non-measurable disease. Percentage of participants with objective response were reported in this outcome measure.
Duration of Response (DOR): Independent Radiological Review (IRR) Assessment
IRR assessed DOR was defined as the time (in months) from the date of first documented objective tumor response (CR or PR) that was subsequently confirmed to the first documented objective tumor progression or death due to any cause, whichever occurred first. According to Choi criteria, CR was defined as disappearance of all target and non-target lesions and no new lesions. PR was defined as a decrease of >=10 percent in tumor size or a decrease in tumor density (HU) of 15 percent or more on CT with no new lesions and no obvious progression of non-measurable disease.
Time to Tumor Response (TTR): Independent Radiological Review (IRR) Assessment
IRR assessed TTR was defined as the time (in months) from date of enrollment in study until first documentation of objective tumor response (CR or PR) that was subsequently confirmed. TTR was calculated as (first response date minus the date of enrollment plus 1) divided by 30.4. According to Choi criteria, CR was defined as disappearance of all target and non-target lesions and no new lesions. PR was defined as a decrease of >=10 percent in tumor size or a decrease in tumor density (HU) of 15 percent or more on CT with no new lesions and no obvious progression of non-measurable disease.
Percentage of Participants With Chromogranin A (CgA) Response
CgA response in participants was defined as having confirmed CgA CR or CgA PR, relative to the population with an elevated baseline CgA value in the blood. CgA CR was defined as decrease from a high baseline value of CgA in the blood to one that fell within the normal range. CgA PR was defined as a decrease of greater than or equal to 50 percent from a high baseline value of CgA. Normal baseline value of CgA in blood was 39.0 ng/mL. Confirmed responses were those that persisted for at least 4 weeks after initial documentation of response. Blood levels of CgA were assessed and percentage of participants with CgA response were reported.
Quality of Life Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)
EORTC QLQ-C30 is a cancer-specific instrument with 30 questions to assess the participant quality of life. First 28 questions used for evaluating 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, nausea and vomiting, pain) and other single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulties). Each question was assessed on 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much); high score represented high level of symptomatology/problem. Last 2 questions used for evaluating global health status (GHS)/quality of life. Each question was assessed on 7-point scale (1=very poor to 7=excellent). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning.
Quality of Life Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Gastrointestinal Related Neuroendocrine Tumours-21 (EORTC QLQ-GI NET 21)
EORTC QLQ-GI-NET 21 was a 21-item questionnaire. These 21 questions assesses endocrine symptoms, gastrointestinal (G.I.) symptoms, treatment related symptoms, social functioning, disease related worries, muscle/bone pain, sexual function, information/communication function and body image. Each item was answered on a 4-point scale: 1 =not at all, 2 =a little, 3 =quite a bit, 4 =very much; where higher scores indicated more severe symptoms/problems. Scores averaged, transformed to 0-100 scale; higher score=more severe symptoms.
Plasma Concentration of Soluble Protein Biomarker (sKIT)
Minimum Observed Plasma Concentration (Ctrough) of Sunitinib and Its Metabolite SU012662
Ctrough is the minimum observed plasma concentration of drug. SU012662 is the metabolite of sunitinib.
Dose-Corrected Trough Plasma Concentration of Sunitinib and Its Metabolite SU012662
Dose-corrected plasma trough concentration is calculated as: trough plasma concentration*(intended dose divided by actual dose). Intended dose was defined as the starting dose in the study and actual dose was defined as the last dose which the participant had received. SU012662 is the metabolite of sunitinib.
Area Under the Curve (AUC24) of Sunitinib and Its Metabolite SU012662
Area under the plasma concentration-time profile from time zero (pre-dose) to 24 hours post-dose. SU012662 is the metabolite of sunitinib.
Oral Clearance (CL/F) of Sunitinib and Its Metabolite SU012662
Clearance is a quantitative measure of the rate at which a drug substance is removed from the body.
Half Maximal Effective Concentration (EC50) of Sunitinib
Concentration of sunitinib in plasma at which 50 percent of the maximum effect was observed.
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 1939 days that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.
Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 1939 days that were absent before treatment or that worsened relative to pre-treatment state. Relatedness to study drug was assessed by the investigator.
Number of Participants With Adverse Events (AEs) According to Severity
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to severity grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. Grade 1 =mild; Grade 2 =moderate; within normal limits, Grade 3 =severe or medically significant but not immediately life-threatening; Grade 4 =life-threatening or disabling; urgent intervention indicated; Grade 5 =death.
Number of Participants With Clinically Significant Laboratory Abnormalities
Following parameters were analyzed for laboratory examination: hematology (hemoglobin, red blood cell count, platelet count, white blood cell count, total neutrophils, basophils, lymphocytes); liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine); electrolytes (sodium, potassium, chloride, calcium, magnesium, phosphate); urinalysis (urine protein), miscellaneous (pregnancy test, Chromogranin A). Clinically significant laboratory abnormalities were identified by the Investigator.
Number of Participants With Change From Baseline in Vital Signs Abnormalities
Following parameters were analyzed for examination of vital signs: systolic and diastolic blood pressure, body temperature and heart rate.
Number of Participants With Increase From Baseline in Corrected QT Interval (QTc)
Number of Participants With Change From Baseline in Physical Examinations Findings
Physical examination included an examination of the general appearance, skin, heart, head, eyes, ears, nose, throat, breasts, abdomen, musculoskeletal, neck, extremities, thyroid and others.
Number of Participants With Change From Baseline in Body Weight
Participants with increase of >=5 percent and decrease of >=5 percent from baseline in body weight were reported in this outcome measure.
Number of Participants With Eastern Co-operative Oncology Group Performance Status (ECOG-PS)
ECOG-PS performance status is used to assess how the disease affects the daily living abilities of the participant. It was measured on 6-point scale ranging from 0-5, where 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory/able to carry out light or sedentary work; 2= ambulatory for more than 50 percent of waking hours and capable of all self-care but unable to carry out any work activities; 3= capable of limited self-care, confined to bed or chair >50 percent of waking hours; 4= completely disabled, not capable of any self-care, totally confined to bed or chair; 5= dead. A higher score indicated greater functional impairment. Only those ECOG-PS categories, in which at least one participant had data at any indicated time point were reported in this outcome measure. Not reported (NR) category included participants with unavailable ECOG performance status.

Full Information

First Posted
January 13, 2012
Last Updated
July 22, 2019
Sponsor
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT01525550
Brief Title
A Study Of The Efficacy And Safety Of Sunitinib In Patients With Advanced Well-Differentiated Pancreatic Neuroendocrine Tumors
Official Title
A SINGLE-ARM OPEN-LABEL INTERNATIONAL MULTI-CENTER STUDY OF THE EFFICACY AND SAFETY OF SUNITINIB MALATE (SU011248, SUTENT (REGISTERED)) IN PATIENTS WITH PROGRESSIVE ADVANCED METASTATIC WELL-DIFFERENTIATED UNRESECTABLE PANCREATIC NEUROENDOCRINE TUMORS
Study Type
Interventional

2. Study Status

Record Verification Date
July 2019
Overall Recruitment Status
Completed
Study Start Date
June 6, 2012 (Actual)
Primary Completion Date
March 19, 2016 (Actual)
Study Completion Date
July 26, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to confirm the safety and efficacy of sunitinib in subjects with unresectable pancreatic neuroendocrine tumors.
Detailed Description
This study is being conducted to meet regulatory post-marketing commitments.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Well-differentiated Pancreatic Neuroendocrine Tumor
Keywords
neuroendocrine tumors, adenoma islet cells, carcinoma islet cells, pancreatic neoplasms, angiogenesis inhibitors, sunitinib, neoplasms, carcinoma, adenoma

7. Study Design

Primary Purpose
Other
Study Phase
Phase 4
Masking
None (Open Label)
Enrollment
106 (Actual)

8. Arms, Groups, and Interventions

Arm Title
sunitinib
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
sunitinib
Intervention Description
Sunitinib capsules will be given orally at continuous daily dosing with a starting dose of 37.5 mg. One cycle is equal to 28 days.
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS): Investigator Assessment
Description
Investigator assessed PFS was defined as the time (in months) from the date of enrollment in study to the date of first documented objective tumor progression or death (due to any cause), whichever occurs first. PFS calculated as (first event date minus date of enrollment plus 1)/30.4. If progression or death was not observed, the participant was censored at the date of the participant's last progression-free tumor assessment prior to the study cut-off date. Progression as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 criteria was defined as: greater than or equal to (>=) 20 percent increase in sum of longest diameter (LD) of target lesions taking as a reference the smallest sum of the LD recorded since the treatment started, or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions. The analysis was performed by Kaplan-Meier method.
Time Frame
Baseline until disease progression or death due to any cause (up to 1226 days)
Secondary Outcome Measure Information:
Title
Progression-Free Survival (PFS): Independent Radiological Review (IRR) Assessment
Description
IRR assessed PFS was defined as the time (in months) from the date of enrollment in study until the date of first documented objective tumor progression or death (due to any cause), whichever occurs first. PFS calculated as (first event date minus date of enrollment plus 1)/30.4. If progression or death was not observed, the participant was censored at the date of the participant's last progression-free tumor assessment prior to the study cut-off date. Progression as per RECIST 1.0 criteria was defined as: >=20 percent increase in sum of LD of target lesions taking as a reference the smallest sum of the LD recorded since the treatment started, or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions. The analysis was performed by Kaplan-Meier method.
Time Frame
Baseline until disease progression or death due to any cause (up to 1226 days)
Title
Time to Tumor Progression (TTP): Investigator Assessment
Description
Investigator assessed TTP was defined as the time (in months) from the date of enrollment in study until the date of first documentation of objective tumor progression. TTP calculated as (first event date minus date of enrollment plus 1)/30.4. Progression as per RECIST 1.0 was defined as >=20 percent increase in sum of LD of target lesions taking as a reference the smallest sum of the LD recorded since the treatment started, or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions. The analysis was performed by Kaplan-Meier method.
Time Frame
Baseline until first documented tumor progression (up to 1226 days)
Title
Overall Survival (OS)
Description
OS was defined as the time (in months) from date of enrollment in study to the date of death due to any cause. If death was not observed, the participant was censored at the earliest of the last date the participant was known to be alive or the end of study. The analysis was performed by Kaplan-Meier method.
Time Frame
Baseline until death or end of study (up to 1939 days)
Title
Percentage of Participants With Objective Response (OR): Investigator Assessment
Description
Investigator assessed OR in participants was defined as having a complete response (CR) or partial response (PR) according to RECIST 1.0 and sustained for at least 4 weeks. CR was defined as disappearance of all target and non-target lesions. PR was defined as >=30 percent decrease in the sum of the LD of the target lesions taking as a reference the baseline sum LD. Percentage of participants with investigator assessed OR were reported.
Time Frame
Baseline until disease progression or death due to any cause (up to 1226 days)
Title
Duration of Response (DOR): Investigator Assessment
Description
Investigator assessed DOR was defined as the time (in months) from the date of first documented objective tumor response (CR or PR), that was subsequently confirmed, to the first documented objective tumor progression or death due to any cause, whichever occurred first. According to RECIST 1.0, CR was defined as disappearance of all target and non-target lesions. PR was defined as >=30 percent decrease in the sum of the LD of the target lesions taking as a reference the baseline sum LD. Progression as per RECIST version 1.0 was defined as >=20 percent increase in sum of LD of target lesions taking as a reference the smallest sum of the LD recorded since the treatment started, or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions.
Time Frame
Baseline until disease progression or death due to any cause (up to 1226 days)
Title
Time to Tumor Response (TTR): Investigator Assessment
Description
Investigator assessed TTR was defined as the time (in months) from date of enrollment in study until date of first documentation of objective tumor response (CR or PR) that was subsequently confirmed. TTR was calculated as (first response date minus the date of enrollment plus 1) divided by 30.4. As per RECIST 1.0, CR was defined as disappearance of all target and non-target lesions and PR was defined as >=30 percent decrease in the sum of the LD of the target lesions taking as a reference the baseline sum LD.
Time Frame
Baseline until first documented objective tumor response (up to 1226 days)
Title
Percentage of Participants With Objective Response (OR): Independent Radiological Review (IRR) Assessment
Description
IRR assessed OR in participants was defined as having a CR or PR according to Choi criteria and sustained for at least 4 weeks. According to Choi criteria, CR was defined as disappearance of all target and non-target lesions and no new lesions. PR was defined as a decrease of >=10 percent in tumor size or a decrease in tumor density (HU) of 15 percent or more on Computed tomography (CT) with no new lesions and no obvious progression of non-measurable disease. Percentage of participants with objective response were reported in this outcome measure.
Time Frame
Baseline until disease progression or death due to any cause (up to 1226 days)
Title
Duration of Response (DOR): Independent Radiological Review (IRR) Assessment
Description
IRR assessed DOR was defined as the time (in months) from the date of first documented objective tumor response (CR or PR) that was subsequently confirmed to the first documented objective tumor progression or death due to any cause, whichever occurred first. According to Choi criteria, CR was defined as disappearance of all target and non-target lesions and no new lesions. PR was defined as a decrease of >=10 percent in tumor size or a decrease in tumor density (HU) of 15 percent or more on CT with no new lesions and no obvious progression of non-measurable disease.
Time Frame
Baseline until disease progression or death due to any cause (up to 1226 days)
Title
Time to Tumor Response (TTR): Independent Radiological Review (IRR) Assessment
Description
IRR assessed TTR was defined as the time (in months) from date of enrollment in study until first documentation of objective tumor response (CR or PR) that was subsequently confirmed. TTR was calculated as (first response date minus the date of enrollment plus 1) divided by 30.4. According to Choi criteria, CR was defined as disappearance of all target and non-target lesions and no new lesions. PR was defined as a decrease of >=10 percent in tumor size or a decrease in tumor density (HU) of 15 percent or more on CT with no new lesions and no obvious progression of non-measurable disease.
Time Frame
Baseline until first documented objective tumor response (up to 1226 days)
Title
Percentage of Participants With Chromogranin A (CgA) Response
Description
CgA response in participants was defined as having confirmed CgA CR or CgA PR, relative to the population with an elevated baseline CgA value in the blood. CgA CR was defined as decrease from a high baseline value of CgA in the blood to one that fell within the normal range. CgA PR was defined as a decrease of greater than or equal to 50 percent from a high baseline value of CgA. Normal baseline value of CgA in blood was 39.0 ng/mL. Confirmed responses were those that persisted for at least 4 weeks after initial documentation of response. Blood levels of CgA were assessed and percentage of participants with CgA response were reported.
Time Frame
Baseline until CgA response or death due to any cause (up to 1226 days)
Title
Quality of Life Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)
Description
EORTC QLQ-C30 is a cancer-specific instrument with 30 questions to assess the participant quality of life. First 28 questions used for evaluating 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, nausea and vomiting, pain) and other single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulties). Each question was assessed on 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much); high score represented high level of symptomatology/problem. Last 2 questions used for evaluating global health status (GHS)/quality of life. Each question was assessed on 7-point scale (1=very poor to 7=excellent). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning.
Time Frame
Day 1 of Cycle 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, End of treatment (up to maximum duration of 1226 days)
Title
Quality of Life Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Gastrointestinal Related Neuroendocrine Tumours-21 (EORTC QLQ-GI NET 21)
Description
EORTC QLQ-GI-NET 21 was a 21-item questionnaire. These 21 questions assesses endocrine symptoms, gastrointestinal (G.I.) symptoms, treatment related symptoms, social functioning, disease related worries, muscle/bone pain, sexual function, information/communication function and body image. Each item was answered on a 4-point scale: 1 =not at all, 2 =a little, 3 =quite a bit, 4 =very much; where higher scores indicated more severe symptoms/problems. Scores averaged, transformed to 0-100 scale; higher score=more severe symptoms.
Time Frame
Day 1 of Cycle 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, End of treatment (up to maximum duration of 1226 days)
Title
Plasma Concentration of Soluble Protein Biomarker (sKIT)
Time Frame
Pre-dose on Day 1 and 15 of Cycle 1, Day 1 of Cycle 2, 3 and every 2 cycles thereafter (Cycle 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43), End of Treatment (up to maximum duration of 1226 days)
Title
Minimum Observed Plasma Concentration (Ctrough) of Sunitinib and Its Metabolite SU012662
Description
Ctrough is the minimum observed plasma concentration of drug. SU012662 is the metabolite of sunitinib.
Time Frame
Pre-dose on Day 15 of Cycle 1, Day 1 of Cycle 2, 3 and 5
Title
Dose-Corrected Trough Plasma Concentration of Sunitinib and Its Metabolite SU012662
Description
Dose-corrected plasma trough concentration is calculated as: trough plasma concentration*(intended dose divided by actual dose). Intended dose was defined as the starting dose in the study and actual dose was defined as the last dose which the participant had received. SU012662 is the metabolite of sunitinib.
Time Frame
Pre dose on Day 15 of Cycle 1, Day 1 of Cycle 2, 3 and 5
Title
Area Under the Curve (AUC24) of Sunitinib and Its Metabolite SU012662
Description
Area under the plasma concentration-time profile from time zero (pre-dose) to 24 hours post-dose. SU012662 is the metabolite of sunitinib.
Time Frame
Pre-dose (0 hour) and at multiple time points (up to 24 hours) post dose on Day 15 of Cycle 1, Day 1 of Cycle 2, 3 and 5 (each cycle 28 days)
Title
Oral Clearance (CL/F) of Sunitinib and Its Metabolite SU012662
Description
Clearance is a quantitative measure of the rate at which a drug substance is removed from the body.
Time Frame
Pre dose on Day 15 of Cycle 1, Day 1 of Cycle 2, 3 and 5 (each cycle 28 days)
Title
Half Maximal Effective Concentration (EC50) of Sunitinib
Description
Concentration of sunitinib in plasma at which 50 percent of the maximum effect was observed.
Time Frame
Pre dose on Day 15 of Cycle 1, Day 1 of Cycle 2, 3 and 5 (each cycle 28 days)
Title
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 1939 days that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.
Time Frame
Baseline up to 1939 days
Title
Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 1939 days that were absent before treatment or that worsened relative to pre-treatment state. Relatedness to study drug was assessed by the investigator.
Time Frame
Baseline up to 1939 days
Title
Number of Participants With Adverse Events (AEs) According to Severity
Description
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to severity grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. Grade 1 =mild; Grade 2 =moderate; within normal limits, Grade 3 =severe or medically significant but not immediately life-threatening; Grade 4 =life-threatening or disabling; urgent intervention indicated; Grade 5 =death.
Time Frame
Baseline up to 1939 days
Title
Number of Participants With Clinically Significant Laboratory Abnormalities
Description
Following parameters were analyzed for laboratory examination: hematology (hemoglobin, red blood cell count, platelet count, white blood cell count, total neutrophils, basophils, lymphocytes); liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine); electrolytes (sodium, potassium, chloride, calcium, magnesium, phosphate); urinalysis (urine protein), miscellaneous (pregnancy test, Chromogranin A). Clinically significant laboratory abnormalities were identified by the Investigator.
Time Frame
Baseline up to 1939 days
Title
Number of Participants With Change From Baseline in Vital Signs Abnormalities
Description
Following parameters were analyzed for examination of vital signs: systolic and diastolic blood pressure, body temperature and heart rate.
Time Frame
Baseline up to 1939 days
Title
Number of Participants With Increase From Baseline in Corrected QT Interval (QTc)
Time Frame
Baseline up to 1939 days
Title
Number of Participants With Change From Baseline in Physical Examinations Findings
Description
Physical examination included an examination of the general appearance, skin, heart, head, eyes, ears, nose, throat, breasts, abdomen, musculoskeletal, neck, extremities, thyroid and others.
Time Frame
Baseline up to 1939 days
Title
Number of Participants With Change From Baseline in Body Weight
Description
Participants with increase of >=5 percent and decrease of >=5 percent from baseline in body weight were reported in this outcome measure.
Time Frame
Baseline up to 1939 days
Title
Number of Participants With Eastern Co-operative Oncology Group Performance Status (ECOG-PS)
Description
ECOG-PS performance status is used to assess how the disease affects the daily living abilities of the participant. It was measured on 6-point scale ranging from 0-5, where 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory/able to carry out light or sedentary work; 2= ambulatory for more than 50 percent of waking hours and capable of all self-care but unable to carry out any work activities; 3= capable of limited self-care, confined to bed or chair >50 percent of waking hours; 4= completely disabled, not capable of any self-care, totally confined to bed or chair; 5= dead. A higher score indicated greater functional impairment. Only those ECOG-PS categories, in which at least one participant had data at any indicated time point were reported in this outcome measure. Not reported (NR) category included participants with unavailable ECOG performance status.
Time Frame
Day 1 of Cycle 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, End of treatment (up to maximum duration of 1226 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically or cytologically proven diagnosis of well-differentiated pancreatic neuroendocrine tumor (according to World Health Organization [WHO 2000] classification). Disease progression within 12 months prior to study enrollment. Disease that is not amenable to surgery, radiation, or combined modality therapy with curative intent. Exclusion Criteria: Patients with poorly differentiated pancreatic neuroendocrine tumors (according to WHO 2000 classification). Prior treatment with any tyrosine kinase inhibitors, anti vascular endothelial growth factor (VEGF) angiogenesis inhibitors, non VEGF targeted angiogenesis inhibitors, or mammalian target of rapamycin (mTOR) inhibitors.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Univeristy of California
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Barwon Health - University Hospital Geelong
City
Geelong
State/Province
Victoria
ZIP/Postal Code
3220
Country
Australia
Facility Name
Cliniques Universitaires Saint-Luc, Gastroenterologie
City
Bruxelles
State/Province
Brussels Gewest
ZIP/Postal Code
1200
Country
Belgium
Facility Name
China-Japan Friendship Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100029
Country
China
Facility Name
307 Hospital of PLA
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100071
Country
China
Facility Name
Beijing Cancer Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100142
Country
China
Facility Name
Nanjing Bayi Hospital
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210002
Country
China
Facility Name
West China Hospital of Sichuan University
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
ZIP/Postal Code
200032
Country
China
Facility Name
Zhongshan Hospital Fudan University
City
Shanghai
ZIP/Postal Code
200032
Country
China
Facility Name
Masarykuv onkologicky ustav
City
Brno
ZIP/Postal Code
656 53
Country
Czechia
Facility Name
Fakultni poliklinika
City
Praha 2
ZIP/Postal Code
128 08
Country
Czechia
Facility Name
Vseobecna Fakultni Nemocnice v Praze
City
Praha 2
ZIP/Postal Code
128 08
Country
Czechia
Facility Name
Hôpital Beaujon
City
Clichy Cedex
ZIP/Postal Code
92118
Country
France
Facility Name
Semmelweis Egyetem/II. Sz. Belgyogyaszati Klinika
City
Budapest
ZIP/Postal Code
1088
Country
Hungary
Facility Name
Tata Memorial Hospital
City
Mumbai
State/Province
Maharashtra
ZIP/Postal Code
400012
Country
India
Facility Name
IEO Istituto Europeo di Oncologia, IRCCS
City
Milano
ZIP/Postal Code
20141
Country
Italy
Facility Name
Kyushu University Hospital
City
Fukuoka-shi
State/Province
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Facility Name
National Cancer Center Hospital
City
Chuo-ku
State/Province
Tokyo
ZIP/Postal Code
104-0045
Country
Japan
Facility Name
Oslo Universitetssykehus HF, Rikshospitalet
City
Oslo
ZIP/Postal Code
0372
Country
Norway
Facility Name
Centrul de Oncologie Sf. Nectarie
City
Craiova
State/Province
Dolj
ZIP/Postal Code
200347
Country
Romania
Facility Name
Institutul Clinic Fundeni, Centrul de Gastroenterologie si Hepatologie
City
Bucuresti
ZIP/Postal Code
022328
Country
Romania
Facility Name
Narodny Onkologicky ustav
City
Bratislava
ZIP/Postal Code
833 10
Country
Slovakia
Facility Name
Wits Clinical Research
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
2193
Country
South Africa
Facility Name
Hospital Universitario Madrid Sanchinarro - Centro Integral Oncológico Clara Campal (CIOCC)
City
Madrid
ZIP/Postal Code
28050
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Citations:
PubMed Identifier
33411058
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.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A6181202&StudyName=A%20Study%20Of%20The%20Efficacy%20And%20Safety%20Of%20Sunitinib%20In%20Patients%20With%20Advanced%20Well-Differentiated%20Pancreatic%20Neuroendocrine%20Tumors
Description
To obtain contact information for a study center near you, click here.

Learn more about this trial

A Study Of The Efficacy And Safety Of Sunitinib In Patients With Advanced Well-Differentiated Pancreatic Neuroendocrine Tumors

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