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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01525550
First Posted: February 3, 2012
Last Update Posted: May 19, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Pfizer
  Purpose
The purpose of this study is to confirm the safety and efficacy of sunitinib in subjects with unresectable pancreatic neuroendocrine tumors.

Condition Intervention Phase
Well-differentiated Pancreatic Neuroendocrine Tumor Drug: sunitinib Phase 4

Study Type: Interventional
Study Design: Masking: None (Open Label)
Primary Purpose: Other
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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Progression-Free Survival (PFS): Investigator Assessment [ Time Frame: Baseline until disease progression or death due to any cause (up to 1226 days) ]
    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 in the absence of progression. 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 [ Time Frame: Baseline until disease progression or death due to any cause (up to 1226 days) ]
    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 in the absence of progression. 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 [ Time Frame: Baseline until first documented tumor progression (up to 1226 days) ]
    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) [ Time Frame: Baseline until death or study cut-off (up to 5 years) ]
    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 study cut-off date. The analysis was performed by Kaplan-Meier method.

  • Percentage of Participants With Objective Response (OR): Investigator Assessment [ Time Frame: Baseline until disease progression or death due to any cause (up to 1226 days) ]
    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 [ Time Frame: Baseline until disease progression or death due to any cause (up to 1226 days) ]
    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 [ Time Frame: Baseline until first documented objective tumor response (up to 1226 days) ]
    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 [ Time Frame: Baseline until disease progression or death due to any cause (up to 1226 days) ]
    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 [ Time Frame: Baseline until disease progression or death due to any cause (up to 1226 days) ]
    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 [ Time Frame: Baseline until first documented objective tumor response (up to 1226 days) ]
    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 [ Time Frame: Baseline until CgA response or death due to any cause (up to 1226 days) ]
    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) [ 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) ]
    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) [ 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) ]
    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) [ 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 1226 days) ]
  • Plasma Concentration (Ctrough) of Sunitinib and Its Metabolite SU012662 [ Time Frame: Pre-dose on Day 15 of Cycle 1, Day 1 of Cycle 2, 3 and 5 ]
    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 [ Time Frame: Pre dose on Day 15 of Cycle 1, Day 1 of Cycle 2, 3 and 5 ]
    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 sunitininb.

  • Area Under the Curve (AUC24) of Sunitinib and Its Metabolite SU012662 [ 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) ]
    Area under the plasma concentration-time profile from time zero (pre-dose) to 24 hours post-dose. SU012662 is the metabolite of sunitininb.

  • Oral Clearance (CL/F) of Sunitinib and Its Metabolite SU012662 [ Time Frame: Pre dose on Day 15 of Cycle 1, Day 1 of Cycle 2, 3 and 5 (each cycle 28 days) ]
    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 [ Time Frame: Pre dose on Day 15 of Cycle 1, Day 1 of Cycle 2, 3 and 5 (each cycle 28 days) ]
    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) [ Time Frame: Baseline up to 1226 days ]
    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 1226 days that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs.

  • Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 1226 days ]
    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 1226 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 [ Time Frame: Baseline up to 1226 days ]
    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 [ Time Frame: Baseline up to 1226 days ]
    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 [ Time Frame: Baseline up to 1226 days ]
    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) [ Time Frame: Baseline up to 1226 days ]
  • Number of Participants With Change From Baseline in Physical Examinations Findings [ Time Frame: Baseline up to 1226 days ]
    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 [ Time Frame: Baseline up to 1226 days ]
    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) [ 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) ]
    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.


Enrollment: 106
Actual Study Start Date: June 6, 2012
Estimated Study Completion Date: June 29, 2018
Primary Completion Date: March 19, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: sunitinib Drug: sunitinib
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.

Detailed Description:
This study is being conducted to meet regulatory post-marketing commitments.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01525550


  Show 27 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01525550     History of Changes
Other Study ID Numbers: A6181202
2011-004363-74 ( EudraCT Number )
First Submitted: January 13, 2012
First Posted: February 3, 2012
Results First Submitted: March 8, 2017
Results First Posted: May 19, 2017
Last Update Posted: May 19, 2017
Last Verified: April 2017

Keywords provided by Pfizer:
neuroendocrine tumors
adenoma islet cells
carcinoma islet cells
pancreatic neoplasms
angiogenesis inhibitors
sunitinib
neoplasms
carcinoma
adenoma

Additional relevant MeSH terms:
Neuroendocrine Tumors
Carcinoid Tumor
Adenoma, Islet Cell
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Adenoma
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Sunitinib
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors