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Trial record 22 of 49 for:    Zollinger-Ellison syndrome

Sorafenib Tosylate in Treating Patients With Progressive Metastatic Neuroendocrine Tumors

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.
 
ClinicalTrials.gov Identifier: NCT00131911
Recruitment Status : Completed
First Posted : August 19, 2005
Results First Posted : November 17, 2014
Last Update Posted : November 17, 2014
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Gastrinoma
Glucagonoma
Insulinoma
Metastatic Gastrointestinal Carcinoid Tumor
Neuroendocrine Tumor
Pancreatic Polypeptide Tumor
Recurrent Gastrointestinal Carcinoid Tumor
Recurrent Islet Cell Carcinoma
Somatostatinoma
WDHA Syndrome
Intervention Drug: sorafenib tosylate
Enrollment 93
Recruitment Details Between June 21, 2005 and September 15, 2006, a total of 93 (51 carcinoid, 42 islet cell) patients initiated treatment on this study.
Pre-assignment Details One carcinoid patient canceled prior to treatment and was excluded from all analyses.
Arm/Group Title Group A (Patients With Carcinoid Tumors) Group B (Islet Cell and Other Neuroendocrine Tumors)
Hide Arm/Group Description Patients receive 400 mg oral sorafenib twice daily on days 1-28. Patients receive 400 mg oral sorafenib twice daily on days 1-28.
Period Title: Overall Study
Started 51 42
Completed 50 42
Not Completed 1 0
Reason Not Completed
Withdrawal by Subject             1             0
Arm/Group Title Group A (Patients With Carcinoid Tumors) Group B (Islet Cell and Other Neuroendocrine Tumors) Total
Hide Arm/Group Description Patients receive 400 mg oral sorafenib twice daily on days 1-28. Patients receive 400 mg oral sorafenib twice daily on days 1-28. Total of all reporting groups
Overall Number of Baseline Participants 51 42 93
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 51 participants 42 participants 93 participants
60
(38 to 82)
56.5
(26 to 78)
59
(26 to 82)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 42 participants 93 participants
Female
28
  54.9%
21
  50.0%
49
  52.7%
Male
23
  45.1%
21
  50.0%
44
  47.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 51 participants 42 participants 93 participants
51 42 93
1.Primary Outcome
Title Confirmed Response Rate
Hide Description

Confirmed response rate was defined using Response Evaluation Criteria In Solid Tumors (RECIST). A confirmed response is defined as a complete response (CR) or partial response (PR) observed on subsequent scans at least 4 weeks apart. Confirmed response rate was estimated by the number of successes divided by the total number of evaluable patients. > > Complete Response (CR) is defined as the disappearance of all target lesions. > Partial Response (PR) is defined as a 30% decrease in sum of longest diameter of target lesions; >

> We report the percentage of patients with a confirmed response and a 95% confidence interval estimated by the Duffy and Santner method.

Time Frame Duration of Treatment (Up to 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Nine of the 50 carcinoid patients and 6 of the 42 Islet cell patients did not continue treatment past cycle 1. Therefore, these patients were not evaluated on consecutive cycles and were excluded from this endpoint.
Arm/Group Title Group A (Patients With Carcinoid Tumors) Group B (Islet Cell and Other Neuroendocrine Tumors)
Hide Arm/Group Description:
Patients receive 400 mg oral sorafenib twice daily on days 1-28.
Patients receive 400 mg oral sorafenib twice daily on days 1-28.
Overall Number of Participants Analyzed 41 36
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
10
(3 to 24)
14
(6 to 32)
2.Secondary Outcome
Title Toxicity
Hide Description For this secondary endpoint, toxicity is defined as a grade 3 or higher adverse events that is classified as either possibly, probably, or definitely related to study treatment. The assignment of attribution to study treatment and grade (or degree of severity) of the adverse event are classified using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The number of participants reporting a grade 3 or higher toxicity are reported.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group A (Patients With Carcinoid Tumors) Group B (Islet Cell and Other Neuroendocrine Tumors)
Hide Arm/Group Description:
Patients receive 400 mg oral sorafenib twice daily on days 1-28.
Patients receive 400 mg oral sorafenib twice daily on days 1-28.
Overall Number of Participants Analyzed 50 42
Measure Type: Number
Unit of Measure: participants
Grade 3 Toxicity 37 25
Grade 4 or Grade 5 Toxicity 5 2
3.Secondary Outcome
Title Overall Survival
Hide Description Overall survival (OS) was defined as the time from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.
Time Frame From registration to death (up to 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group A (Patients With Carcinoid Tumors) Group B (Islet Cell and Other Neuroendocrine Tumors)
Hide Arm/Group Description:
Patients receive 400 mg oral sorafenib twice daily on days 1-28.
Patients receive 400 mg oral sorafenib twice daily on days 1-28.
Overall Number of Participants Analyzed 50 42
Median (95% Confidence Interval)
Unit of Measure: months
25.6
(15.5 to 30.2)
NA [1] 
(NA to NA)
[1]
At the time of analysis, a sufficient number of events had not been recorded to estimate.
4.Secondary Outcome
Title Progression Free Survival
Hide Description Progression was defined using Response Evaluation Criteria In Solid Tumors (RECIST) as a 20% increase in the su of longest diameter of target lesions. Progression free survival (PFS) was defined as the time from registration to progression or death of any cause. Participants who were progression free were censored at the date of their most recent disease assessment. The median PFS with 95% CI was estimated using the Kaplan Meier method.
Time Frame Time from registration to progression or death (up to 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group A (Patients With Carcinoid Tumors) Group B (Islet Cell and Other Neuroendocrine Tumors)
Hide Arm/Group Description:
Patients receive 400 mg oral sorafenib twice daily on days 1-28.
Patients receive 400 mg oral sorafenib twice daily on days 1-28.
Overall Number of Participants Analyzed 50 42
Median (95% Confidence Interval)
Unit of Measure: months
9.1
(5.7 to 12.7)
12.7
(8.3 to 19.9)
5.Secondary Outcome
Title Duration of Response
Hide Description Duration of response (DOR) was defined as the time from attaining a response (PR or CR) to the date of progression. Participants without progression were censored at the date of their most recent disease assessment. The median DOR was estimated using simple summary statistics.
Time Frame Time from response to progression (up to 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
There were 4 confirmed responses in Group A and 5 confirmed responses in Group B used in analyzing this endpoint.
Arm/Group Title Group A (Patients With Carcinoid Tumors) Group B (Islet Cell and Other Neuroendocrine Tumors)
Hide Arm/Group Description:
Patients receive 400 mg oral sorafenib twice daily on days 1-28.
Patients receive 400 mg oral sorafenib twice daily on days 1-28.
Overall Number of Participants Analyzed 4 5
Median (Full Range)
Unit of Measure: months
6.7
(3.7 to 9.2)
9.2
(3.7 to 32)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title All Patients
Hide Arm/Group Description Patients receive 400 mg oral sorafenib twice daily on days 1-28.
All-Cause Mortality
All Patients
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
All Patients
Affected / at Risk (%) # Events
Total   52/93 (55.91%)    
Blood and lymphatic system disorders   
Hemoglobin decreased  1  3/93 (3.23%)  3
Endocrine disorders   
Hypothyroidism  1  1/93 (1.08%)  1
Gastrointestinal disorders   
Abdominal distension  1  1/93 (1.08%)  1
Abdominal pain  1  18/93 (19.35%)  22
Ascites  1  3/93 (3.23%)  3
Constipation  1  3/93 (3.23%)  3
Diarrhea  1  5/93 (5.38%)  5
Dry mouth  1  1/93 (1.08%)  1
Duodenal hemorrhage  1  1/93 (1.08%)  1
Duodenal perforation  1  1/93 (1.08%)  1
Duodenal ulcer  1  1/93 (1.08%)  1
Ear, nose and throat examination abnormal  1  4/93 (4.30%)  4
Gastrointestinal disorder  1  2/93 (2.15%)  2
Intra-abdominal hemorrhage  1  1/93 (1.08%)  1
Lower gastrointestinal hemorrhage  1  1/93 (1.08%)  1
Mucositis oral  1  1/93 (1.08%)  2
Nausea  1  13/93 (13.98%)  15
Rectal fistula  1  1/93 (1.08%)  1
Small intestinal obstruction  1  3/93 (3.23%)  5
Small intestinal perforation  1  1/93 (1.08%)  1
Vomiting  1  8/93 (8.60%)  9
General disorders   
Chills  1  1/93 (1.08%)  1
Disease progression  1  1/93 (1.08%)  1
Edema limbs  1  3/93 (3.23%)  3
Fatigue  1  15/93 (16.13%)  15
Fever  1  4/93 (4.30%)  4
Localized edema  1  1/93 (1.08%)  1
Hepatobiliary disorders   
Cholecystitis  1  1/93 (1.08%)  1
Gallbladder pain  1  1/93 (1.08%)  1
Hepatobiliary disease  1  1/93 (1.08%)  1
Immune system disorders   
Hypersensitivity  1  1/93 (1.08%)  1
Infections and infestations   
Bladder infection  1  1/93 (1.08%)  1
Pleural infection  1  1/93 (1.08%)  3
Pneumonia  1  1/93 (1.08%)  1
Sepsis  1  1/93 (1.08%)  1
Skin infection  1  1/93 (1.08%)  4
Investigations   
Alanine aminotransferase increased  1  1/93 (1.08%)  1
Alkaline phosphatase increased  1  3/93 (3.23%)  3
Aspartate aminotransferase increased  1  4/93 (4.30%)  4
Blood bilirubin increased  1  2/93 (2.15%)  2
Creatinine increased  1  1/93 (1.08%)  1
Leukocyte count decreased  1  1/93 (1.08%)  1
Lymphocyte count decreased  1  1/93 (1.08%)  1
Neutrophil count decreased  1  1/93 (1.08%)  1
Weight gain  1  1/93 (1.08%)  1
Weight loss  1  1/93 (1.08%)  1
Metabolism and nutrition disorders   
Alkalosis  1  1/93 (1.08%)  1
Anorexia  1  10/93 (10.75%)  11
Blood glucose increased  1  2/93 (2.15%)  2
Dehydration  1  6/93 (6.45%)  7
Serum albumin decreased  1  3/93 (3.23%)  3
Serum calcium decreased  1  2/93 (2.15%)  2
Serum phosphate decreased  1  1/93 (1.08%)  1
Serum potassium decreased  1  3/93 (3.23%)  3
Serum potassium increased  1  3/93 (3.23%)  3
Serum sodium decreased  1  3/93 (3.23%)  6
Serum sodium increased  1  1/93 (1.08%)  1
Serum triglycerides increased  1  1/93 (1.08%)  1
Musculoskeletal and connective tissue disorders   
Arthralgia  1  2/93 (2.15%)  2
Back pain  1  3/93 (3.23%)  3
Bone pain  1  1/93 (1.08%)  1
Myalgia  1  6/93 (6.45%)  6
Neck pain  1  1/93 (1.08%)  1
Pain in extremity  1  1/93 (1.08%)  1
Nervous system disorders   
Dizziness  1  2/93 (2.15%)  2
Headache  1  2/93 (2.15%)  2
Psychiatric disorders   
Confusion  1  1/93 (1.08%)  1
Insomnia  1  1/93 (1.08%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnea  1  6/93 (6.45%)  7
Pneumonitis  1  1/93 (1.08%)  1
Respiratory tract hemorrhage  1  1/93 (1.08%)  1
Voice alteration  1  2/93 (2.15%)  2
Skin and subcutaneous tissue disorders   
Alopecia  1  2/93 (2.15%)  3
Hand-and-foot syndrome  1  4/93 (4.30%)  4
Rash acneiform  1  4/93 (4.30%)  4
Rash desquamating  1  2/93 (2.15%)  2
Skin disorder  1  1/93 (1.08%)  1
Skin ulceration  1  1/93 (1.08%)  1
Sweating  1  3/93 (3.23%)  3
Vascular disorders   
Flushing  1  1/93 (1.08%)  1
Hemorrhage  1  1/93 (1.08%)  1
Hot flashes  1  1/93 (1.08%)  1
Hypotension  1  2/93 (2.15%)  2
Thrombosis  1  2/93 (2.15%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 6
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
All Patients
Affected / at Risk (%) # Events
Total   90/93 (96.77%)    
Blood and lymphatic system disorders   
Blood disorder  1  2/93 (2.15%)  7
Hemoglobin decreased  1  18/93 (19.35%)  63
Cardiac disorders   
Atrial fibrillation  1  2/93 (2.15%)  2
Atrial flutter  1  1/93 (1.08%)  1
Cardiac disorder  1  1/93 (1.08%)  1
Sinus bradycardia  1  1/93 (1.08%)  1
Ear and labyrinth disorders   
Hearing test abnormal  1  1/93 (1.08%)  3
Endocrine disorders   
Hypothyroidism  1  1/93 (1.08%)  37
Eye disorders   
Diplopia  1  1/93 (1.08%)  1
Eye disorder  1  1/93 (1.08%)  2
Retinal detachment  1  1/93 (1.08%)  1
Vision blurred  1  1/93 (1.08%)  1
Watering eyes  1  1/93 (1.08%)  1
Gastrointestinal disorders   
Abdominal distension  1  5/93 (5.38%)  16
Abdominal pain  1  34/93 (36.56%)  99
Anal pain  1  1/93 (1.08%)  2
Ascites  1  2/93 (2.15%)  2
Colitis  1  1/93 (1.08%)  1
Constipation  1  7/93 (7.53%)  11
Diarrhea  1  65/93 (69.89%)  467
Dry mouth  1  4/93 (4.30%)  7
Dyspepsia  1  10/93 (10.75%)  40
Ear, nose and throat examination abnormal  1  35/93 (37.63%)  99
Flatulence  1  9/93 (9.68%)  88
Gingival pain  1  1/93 (1.08%)  4
Hemorrhoids  1  1/93 (1.08%)  2
Mucositis oral  1  1/93 (1.08%)  1
Nausea  1  45/93 (48.39%)  121
Oral hemorrhage  1  1/93 (1.08%)  1
Rectal fistula  1  1/93 (1.08%)  6
Rectal hemorrhage  1  1/93 (1.08%)  1
Rectal pain  1  2/93 (2.15%)  5
Small intestinal perforation  1  1/93 (1.08%)  1
Vomiting  1  22/93 (23.66%)  31
General disorders   
Chest pain  1  3/93 (3.23%)  3
Chills  1  5/93 (5.38%)  8
Edema limbs  1  8/93 (8.60%)  10
Fatigue  1  63/93 (67.74%)  306
Fever  1  8/93 (8.60%)  10
Localized edema  1  3/93 (3.23%)  3
Pain  1  4/93 (4.30%)  27
Hepatobiliary disorders   
Hepatic failure  1  1/93 (1.08%)  1
Immune system disorders   
Hypersensitivity  1  1/93 (1.08%)  1
Infections and infestations   
Abdominal infection  1  4/93 (4.30%)  7
Anal infection  1  1/93 (1.08%)  1
Bladder infection  1  1/93 (1.08%)  1
Hepatic infection  1  1/93 (1.08%)  1
Infection  1  1/93 (1.08%)  1
Pneumonia  1  2/93 (2.15%)  2
Prostate infection  1  1/93 (1.08%)  1
Sinusitis  1  1/93 (1.08%)  1
Skin infection  1  4/93 (4.30%)  16
Upper respiratory infection  1  4/93 (4.30%)  4
Injury, poisoning and procedural complications   
Wound dehiscence  1  1/93 (1.08%)  2
Investigations   
Alanine aminotransferase increased  1  21/93 (22.58%)  88
Alkaline phosphatase increased  1  28/93 (30.11%)  163
Aspartate aminotransferase increased  1  32/93 (34.41%)  115
Blood bilirubin increased  1  7/93 (7.53%)  14
Blood corticotrophin decreased  1  1/93 (1.08%)  1
Creatine phosphokinase increased  1  1/93 (1.08%)  1
Creatinine increased  1  14/93 (15.05%)  33
Gamma-glutamyltransferase increased  1  1/93 (1.08%)  1
Laboratory test abnormal  1  2/93 (2.15%)  6
Leukocyte count decreased  1  8/93 (8.60%)  11
Lipase increased  1  1/93 (1.08%)  1
Lymphocyte count decreased  1  7/93 (7.53%)  12
Neutrophil count decreased  1  5/93 (5.38%)  8
Platelet count decreased  1  24/93 (25.81%)  67
Serum cholesterol increased  1  1/93 (1.08%)  1
Weight loss  1  10/93 (10.75%)  27
Metabolism and nutrition disorders   
Alkalosis  1  1/93 (1.08%)  1
Anorexia  1  39/93 (41.94%)  100
Blood bicarbonate decreased  1  7/93 (7.53%)  13
Blood glucose increased  1  11/93 (11.83%)  31
Blood uric acid increased  1  1/93 (1.08%)  1
Dehydration  1  1/93 (1.08%)  1
Serum albumin decreased  1  7/93 (7.53%)  45
Serum calcium decreased  1  11/93 (11.83%)  23
Serum glucose decreased  1  1/93 (1.08%)  1
Serum magnesium increased  1  5/93 (5.38%)  8
Serum phosphate decreased  1  6/93 (6.45%)  9
Serum potassium decreased  1  6/93 (6.45%)  8
Serum potassium increased  1  5/93 (5.38%)  9
Serum sodium decreased  1  7/93 (7.53%)  9
Serum sodium increased  1  5/93 (5.38%)  9
Serum triglycerides increased  1  1/93 (1.08%)  6
Musculoskeletal and connective tissue disorders   
Arthralgia  1  7/93 (7.53%)  17
Arthritis  1  2/93 (2.15%)  2
Back pain  1  7/93 (7.53%)  20
Bone pain  1  3/93 (3.23%)  3
Muscle weakness  1  2/93 (2.15%)  4
Myalgia  1  19/93 (20.43%)  64
Neck pain  1  1/93 (1.08%)  1
Pain in extremity  1  6/93 (6.45%)  7
Nervous system disorders   
Accessory nerve disorder  1  1/93 (1.08%)  10
Dizziness  1  6/93 (6.45%)  16
Dysgeusia  1  3/93 (3.23%)  11
Facial nerve disorder  1  1/93 (1.08%)  1
Headache  1  9/93 (9.68%)  16
Neurological disorder NOS  1  1/93 (1.08%)  1
Peripheral motor neuropathy  1  3/93 (3.23%)  6
Peripheral sensory neuropathy  1  6/93 (6.45%)  8
Syncope  1  1/93 (1.08%)  1
Psychiatric disorders   
Anxiety  1  4/93 (4.30%)  14
Confusion  1  1/93 (1.08%)  2
Depression  1  2/93 (2.15%)  2
Insomnia  1  6/93 (6.45%)  11
Renal and urinary disorders   
Hemoglobin urine positive  1  3/93 (3.23%)  4
Renal failure  1  1/93 (1.08%)  1
Urinary frequency  1  1/93 (1.08%)  2
Reproductive system and breast disorders   
Vaginal pain  1  1/93 (1.08%)  1
Respiratory, thoracic and mediastinal disorders   
Bronchospasm  1  1/93 (1.08%)  2
Cough  1  5/93 (5.38%)  9
Dyspnea  1  23/93 (24.73%)  73
Epistaxis  1  2/93 (2.15%)  2
Pneumonitis  1  1/93 (1.08%)  1
Voice alteration  1  5/93 (5.38%)  27
Skin and subcutaneous tissue disorders   
Alopecia  1  46/93 (49.46%)  246
Dry skin  1  13/93 (13.98%)  29
Hand-and-foot syndrome  1  52/93 (55.91%)  267
Nail disorder  1  3/93 (3.23%)  5
Photosensitivity  1  1/93 (1.08%)  1
Pruritus  1  4/93 (4.30%)  8
Rash acneiform  1  51/93 (54.84%)  184
Rash desquamating  1  15/93 (16.13%)  21
Scalp pain  1  1/93 (1.08%)  1
Skin disorder  1  3/93 (3.23%)  3
Sweating  1  6/93 (6.45%)  11
Vascular disorders   
Flushing  1  6/93 (6.45%)  15
Hot flashes  1  6/93 (6.45%)  12
Hypertension  1  51/93 (54.84%)  189
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 6
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Timothy J. Hobday M.D.
Organization: Mayo Clinic Cancer Center
EMail: Hobday.timothy@mayo.edu
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00131911     History of Changes
Other Study ID Numbers: NCI-2009-00121
MC044H
7046
CDR0000437792
N01CM62205 ( U.S. NIH Grant/Contract )
First Submitted: August 16, 2005
First Posted: August 19, 2005
Results First Submitted: June 19, 2014
Results First Posted: November 17, 2014
Last Update Posted: November 17, 2014