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

• ClinicalTrials.gov Identifier: NCT01121562
• Recruitment Status: Completed
• First Posted: May 12, 2010
• Results First Posted: August 27, 2012
• Last Update Posted: June 30, 2014
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pancreatic Neuroendocrine Tumors
• Intervention: Drug: Sunitinib
• Enrollment: 12

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Sunitinib
Arm/Group Description	Sunitinib 37.5 mg was orally administered once daily in a continuous daily dosing regimen (1 cycle = 4 weeks).
Period Title: Overall Study
Started	12
Completed	0
Not Completed	12
Reason Not Completed
Objective progression or relapse	8
Withdrawal by Subject	1
Adverse Event	1
Sponsor Decision	1
Met study discontinuation criteria	1

Baseline Characteristics

Arm/Group Title		Sunitinib
Arm/Group Description		Sunitinib 37.5 mg was orally administered once daily in a continuous daily dosing regimen (1 cycle = 4 weeks).
Overall Number of Baseline Participants		12
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	12 participants
		54.1 (13.0)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants
	Female	4 33.3%
	Male	8 66.7%

Outcome Measures

1. Primary Outcome

Title	Clinical Benefit Response Rate (CBR)
Description	CBR rate is defined as the percentage of participants with a best overall response of confirmed complete response (CR), confirmed partial response (PR) ,or stable disease (SD) ≥ 24 weeks. Based on RECIST, CR is defined as the disappearance of all target lesions and PR is defined as a greater than or equal to 30% decrease in the sum of the longest dimensions of the target lesion. SD is defined neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest dimensions since the treatment started.
Time Frame	Up to 799 days of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set was defined as the population of all enrolled participants in whom well-differentiated pancreatic neuroendocrine tumor had been diagnosed and who received at least one dose of study medication.

Arm/Group Title	Sunitinib
Arm/Group Description:	Sunitinib 37.5 mg was orally administered once daily in a continuous daily dosing regimen (1 cycle = 4 weeks).
Overall Number of Participants Analyzed	12
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	75.0; (42.8 to 94.5)

2. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	ORR is defined as the percentage of participants with a best overall response of confirmed CR or confirmed PR. Based on the response evaluation criteria in solid tumors (RECIST), CR is defined as the disappearance of all target lesions and PR is defined as a greater than or equal to 30% decrease in the sum of the longest dimensions of the target lesion.
Time Frame	Up to 799 days of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set was defined as the population of all enrolled participants in whom well-differentiated pancreatic neuroendocrine tumor had been diagnosed and who received at least one dose of study medication.

Arm/Group Title	Sunitinib
Arm/Group Description:	Sunitinib 37.5 mg was orally administered once daily in a continuous daily dosing regimen (1 cycle = 4 weeks).
Overall Number of Participants Analyzed	12
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	50.0; (21.1 to 78.9)

3. Secondary Outcome

Title	Tumor Shrinkage
Description	Tumor shrinkage is defined as the percent change from baseline for the sum of the longest diameter of target lesions in participants.
Time Frame	Up to 799 days of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set was defined as the population of all enrolled participants in whom well-differentiated pancreatic neuroendocrine tumor had been diagnosed and who received at least one dose of study medication. "n " in the measured values means number of participants analyzed in the cycle.

Arm/Group Title	Sunitinib
Arm/Group Description:	Sunitinib 37.5 mg was orally administered once daily in a continuous daily dosing regimen (1 cycle = 4 weeks).
Overall Number of Participants Analyzed	12
Mean (Standard Deviation); Unit of Measure: percent change
Cycle 1 (n=1)	-20.0 [1] (NA)
Cycle 2 (n=11)	-14.4 (13.43)
Cycle 3 (n=12)	-18.0 (17.70)
Cycle 5 (n=9)	-26.0 (10.03)
Cycle 7 (n=9)	-28.5 (11.86)
Cycle 9 (n=9)	-31.8 (17.20)
Cycle 11 (n=9)	-36.4 (30.11)
Cycle 13 (n=9)	-28.8 (16.92)
Cycle 14 (n=1)	1.7 [1] (NA)
Cycle 15 (n=7)	-32.5 (17.29)
Cycle 16 (n=1)	-34.7 [1] (NA)
Cycle 17 (n=5)	-38.7 (15.41)
Cycle 18 (n=1)	-43.1 [1] (NA)
Cycle 19 (n=4)	-37.8 (19.21)
Cycle 21 (n=4)	-35.8 (19.19)
Cycle 23 (n=4)	-35.1 (22.82)
Cycle 25 (n=4)	-32.6 (19.64)
Cycle 27 (n=3)	-30.8 (26.68)
Cycle 28 (n=2)	-40.4 (9.72)
Cycle 29 (n=1)	3.3 [1] (NA)
Maximum Reduction (n=12)	-34.8 (28.76)

[1]

Only 1 participant was analyzed in this cycle

4. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	PFS is defined as the time from registration to first documentation of progressive disease (PD) or to death due to any cause, whichever occurs first.
Time Frame	Up to 799 days of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set was defined as the population of all enrolled participants in whom well-differentiated pancreatic neuroendocrine tumor had been diagnosed and who received at least one dose of study medication.

Median PFS had not yet been reached due to short of events.

Arm/Group Title	Sunitinib
Arm/Group Description:	Sunitinib 37.5 mg was orally administered once daily in a continuous daily dosing regimen (1 cycle = 4 weeks).
Overall Number of Participants Analyzed	12
Median (95% Confidence Interval); Unit of Measure: Months
	16.8; (9.3 to 26.2)

5. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall Survival (OS) is defined as the time from registration to documentation of death due to any cause.
Time Frame	Up to 3 years from the last subject registration to the study

Outcome Measure Data

Analysis Population Description

Full Analysis Set was defined as the population of all enrolled participants in whom well-differentiated pancreatic neuroendocrine tumor had been diagnosed and who received at least one dose of study medication.

OS was not analyzed due to short of events.

Arm/Group Title	Sunitinib
Arm/Group Description:	Sunitinib 37.5 mg was orally administered once daily in a continuous daily dosing regimen (1 cycle = 4 weeks).
Overall Number of Participants Analyzed	12
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (22.0 to NA)

[1]

Median OS had not yet been reached due to short of events.

6. Secondary Outcome

Title	Dose-corrected Trough Plasma Concentrations of Sunitinib, SU012662 and Total Drug (Sunitinib + SU012662).
Description	Reference dose is 37.5 mg. Dose-corrected concentration is calculated from the following formula, "observed concentration multiplied by 37.5" over "actual dose". SU012662 is an active metabolite of sunitinib.
Time Frame	Predose of Cycle 1 Day15, Cycle 2 Day1, Cycle 3 Day1, and Cycle 4 Day 1

Outcome Measure Data

Analysis Population Description

The pharmacokinetics analysis set was defined as all participants who had at least one plasma concentration data at trough sampling with steady-state condition. "n" in the measured values means number of participants analyzed.

Arm/Group Title	Sunitinib
Arm/Group Description:	Sunitinib 37.5 mg was orally administered once daily in a continuous daily dosing regimen (1 cycle = 4 weeks).
Overall Number of Participants Analyzed	11
Mean (Standard Deviation); Unit of Measure: nanogram/mL
Sunitinib (Cycle 1 Day 15, n=10)	53.9 (17.6)
Sunitinib (Cycle 2 Day 1, n=2)	41.7 (21.9)
Sunitinib (Cycle 3 Day 1, n=8)	49.9 (19.7)
Sunitinib (Cycle 4 Day 1, n=5)	53.5 (24.6)
SU012662 (Cycle 1 Day 15, n=10)	23.7 (7.00)
SU012662 (Cycle 2 Day 1, n=2)	21.2 (6.36)
SU012662 (Cycle 3 Day 1, n=8)	25.7 (9.14)
SU012662 (Cycle 4 Day 1, n=5)	19.6 (7.44)
Total drug (Cycle 1 Day 15, n=10)	77.5 (20.9)
Total drug (Cycle 2 Day 1, n=2)	62.9 (28.3)
Total drug (Cycle 3 Day 1, n=8)	75.5 (26.5)
Total drug (Cycle 4 Day 1, n=5)	73.0 (28.8)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Sunitinib
Arm/Group Description	Sunitinib 37.5 mg was orally administered once daily in a continuous daily dosing regimen (1 cycle = 4 weeks).
All-Cause Mortality
	Sunitinib
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Sunitinib
	Affected / at Risk (%)
Total	3/12 (25.00%)
Gastrointestinal disorders
Enterocolitis * 1	1/12 (8.33%)
Hepatobiliary disorders
Cholangitis * 1	1/12 (8.33%)
Cholecystitis acute * 1	1/12 (8.33%)
Nervous system disorders
Convulsion * 1	1/12 (8.33%)
Loss of consciousness * 1	1/12 (8.33%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 14.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Sunitinib
	Affected / at Risk (%)
Total	12/12 (100.00%)
Blood and lymphatic system disorders
Anaemia * 1	2/12 (16.67%)
Disseminated intravascular coagulation * 1	1/12 (8.33%)
Neutropenia * 1	2/12 (16.67%)
Thrombocytopenia * 1	1/12 (8.33%)
Cardiac disorders
Left ventricular dysfunction * 1	2/12 (16.67%)
Endocrine disorders
Hypothyroidism * 1	4/12 (33.33%)
Eye disorders
Conjunctival haemorrhage * 1	1/12 (8.33%)
Diplopia * 1	1/12 (8.33%)
Eyelash discolouration * 1	1/12 (8.33%)
Ocular hyperaemia * 1	1/12 (8.33%)
Gastrointestinal disorders
Abdominal distension * 1	1/12 (8.33%)
Abdominal pain * 1	1/12 (8.33%)
Ascites * 1	2/12 (16.67%)
Constipation * 1	1/12 (8.33%)
Diarrhoea * 1	10/12 (83.33%)
Dyspepsia * 1	1/12 (8.33%)
Dysphagia * 1	1/12 (8.33%)
Gastritis * 1	1/12 (8.33%)
Gingivitis * 1	2/12 (16.67%)
Glossitis * 1	1/12 (8.33%)
Haemorrhoids * 1	1/12 (8.33%)
Hypoaesthesia oral * 1	1/12 (8.33%)
Loose tooth * 1	1/12 (8.33%)
Nausea * 1	5/12 (41.67%)
Oral dysaesthesia * 1	2/12 (16.67%)
Periodontitis * 1	1/12 (8.33%)
Reflux oesophagitis * 1	2/12 (16.67%)
Stomatitis * 1	2/12 (16.67%)
Toothache * 1	1/12 (8.33%)
Vomiting * 1	5/12 (41.67%)
General disorders
Face oedema * 1	1/12 (8.33%)
Fatigue * 1	7/12 (58.33%)
Malaise * 1	2/12 (16.67%)
Mucosal inflammation * 1	3/12 (25.00%)
Oedema * 1	4/12 (33.33%)
Oedema peripheral * 1	2/12 (16.67%)
Pyrexia * 1	5/12 (41.67%)
Hepatobiliary disorders
Cholangitis * 1	1/12 (8.33%)
Hepatic failure * 1	1/12 (8.33%)
Infections and infestations
Encephalitis herpes * 1	1/12 (8.33%)
Enteritis infectious * 1	1/12 (8.33%)
Enterocolitis infectious * 1	1/12 (8.33%)
Hordeolum * 1	1/12 (8.33%)
Infected epidermal cyst * 1	1/12 (8.33%)
Nasopharyngitis * 1	5/12 (41.67%)
Oral herpes * 1	1/12 (8.33%)
Pharyngitis * 1	1/12 (8.33%)
Pneumonia * 1	1/12 (8.33%)
Pyoderma * 1	1/12 (8.33%)
Skin candida * 1	1/12 (8.33%)
Trichophytosis * 1	2/12 (16.67%)
Injury, poisoning and procedural complications
Contusion * 1	2/12 (16.67%)
Fall * 1	1/12 (8.33%)
Wound * 1	1/12 (8.33%)
Investigations
Blood alkaline phosphatase increased * 1	1/12 (8.33%)
Blood urine present * 1	1/12 (8.33%)
Electrocardiogram QT prolonged * 1	3/12 (25.00%)
Gamma-glutamyltransferase increased * 1	1/12 (8.33%)
Lipase increased * 1	2/12 (16.67%)
Lymphocyte count decreased * 1	1/12 (8.33%)
Neutrophil count decreased * 1	4/12 (33.33%)
Platelet count decreased * 1	2/12 (16.67%)
Protein urine present * 1	2/12 (16.67%)
Urine output decreased * 1	1/12 (8.33%)
White blood cell count decreased * 1	3/12 (25.00%)
Metabolism and nutrition disorders
Decreased appetite * 1	4/12 (33.33%)
Hyperamylasaemia * 1	1/12 (8.33%)
Hypercholesterolaemia * 1	1/12 (8.33%)
Hypoalbuminaemia * 1	1/12 (8.33%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	1/12 (8.33%)
Back pain * 1	2/12 (16.67%)
Muscle spasms * 1	3/12 (25.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma * 1	1/12 (8.33%)
Nervous system disorders
Dysaesthesia * 1	1/12 (8.33%)
Dysgeusia * 1	5/12 (41.67%)
Headache * 1	7/12 (58.33%)
Hypoaesthesia * 1	1/12 (8.33%)
Psychiatric disorders
Insomnia * 1	1/12 (8.33%)
Renal and urinary disorders
Haematuria * 1	1/12 (8.33%)
Nephrotic syndrome * 1	1/12 (8.33%)
Pollakiuria * 1	1/12 (8.33%)
Proteinuria * 1	2/12 (16.67%)
Reproductive system and breast disorders
Scrotal haematocoele * 1	1/12 (8.33%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	1/12 (8.33%)
Epistaxis * 1	2/12 (16.67%)
Pleural effusion * 1	1/12 (8.33%)
Pneumomediastinum * 1	1/12 (8.33%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform * 1	1/12 (8.33%)
Dry skin * 1	1/12 (8.33%)
Eczema * 1	1/12 (8.33%)
Hair colour changes * 1	1/12 (8.33%)
Nail disorder * 1	1/12 (8.33%)
Onychomadesis * 1	1/12 (8.33%)
Palmar-plantar erythrodysaesthesia syndrome * 1	8/12 (66.67%)
Pruritus * 1	2/12 (16.67%)
Rash * 1	2/12 (16.67%)
Skin discolouration * 1	1/12 (8.33%)
Skin reaction * 1	1/12 (8.33%)
Vascular disorders
Hypertension * 1	8/12 (66.67%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 14.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Results Point of Contact

• Name/Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.
• Phone: 1-800-718-1021
• EMail: ClinicalTrials.gov_Inquiries@pfizer.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ito T, Okusaka T, Nishida T, Yamao K, Igarashi H, Morizane C, Kondo S, Mizuno N, Hara K, Sawaki A, Hashigaki S, Kimura N, Murakami M, Ohki E, Chao RC, Imamura M. Phase II study of sunitinib in Japanese patients with unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumor. Invest New Drugs. 2013 Oct;31(5):1265-74. doi: 10.1007/s10637-012-9910-y. Epub 2012 Dec 27. Erratum In: Invest New Drugs. 2019 Jun;37(3):591.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01121562
• Other Study ID Numbers: A6181193
• First Submitted: May 10, 2010
• First Posted: May 12, 2010
• Results First Submitted: July 1, 2012
• Results First Posted: August 27, 2012
• Last Update Posted: June 30, 2014