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Temozolomide and Pazopanib Hydrochloride in Treating Patients With Advanced Pancreatic Neuroendocrine Tumors That Cannot Be Removed By Surgery

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: NCT01465659
Recruitment Status : Active, not recruiting
First Posted : November 6, 2011
Results First Posted : June 17, 2020
Last Update Posted : June 17, 2020
Sponsor:
Collaborators:
Robert H. Lurie Cancer Center
National Comprehensive Cancer Network
GlaxoSmithKline
Information provided by (Responsible Party):
Northwestern University

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Pancreatic Alpha Cell Carcinoma
Pancreatic Beta Islet Cell Carcinoma
Pancreatic Delta Cell Carcinoma
Pancreatic G-cell Carcinoma
Recurrent Islet Cell Carcinoma
Interventions Drug: temozolomide
Drug: pazopanib hydrochloride
Enrollment 29
Recruitment Details The study was opened to enrollment on November 15th 2011 with the first patient starting treatment December 12th 2011. The study was designed to enroll up to 40 patients with a phase I dose escalation portion and a phase II expansion portion at the determined dose. The study was closed to further enrollment February 27 2019.
Pre-assignment Details  
Arm/Group Title Cohort 1 - Temozolomide 150 mg/m2 and Pazopanib 400 mg Cohort -1 -Temozolomide 100 mg/m2 and Pazopanib 400 mg Cohort -2 - Temozolomide 75 mg/m2 and Pazopanib 400 mg Phase II -Temozolomide 75 mg/m2 and Pazopanib 400 mg
Hide Arm/Group Description

Temozolomide 150 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28

temozolomide: Given PO

pazopanib hydrochloride: Given PO

Temozolomide 100 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28

temozolomide: Given PO

pazopanib hydrochloride: Given PO

Temozolomide 75 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28

temozolomide: Given PO

pazopanib hydrochloride: Given PO

Temozolomide 75mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28

temozolomide: Given PO

pazopanib hydrochloride: Given PO

Period Title: Completed 1 Cycle of Treatment
Started 7 5 6 11
Completed 1 Cycle of Treatment 7 4 6 11
Completed 7 4 6 10
Not Completed 0 1 0 1
Reason Not Completed
Death             0             1             0             0
Adverse Event             0             0             0             1
Period Title: Completed 2 Cycles/Reached 1st Response
Started 7 4 6 10
Attempted 2 Cycles of Treatment 7 4 6 10
Reached 1st Response 7 4 6 10
Assessed to Move on to Next Cycle 7 4 4 10
Completed 5 4 4 9
Not Completed 2 0 2 1
Reason Not Completed
Progressive Disease             1             0             1             1
Adverse Event             1             0             1             0
Period Title: Went on to Cycle 3 and Beyond
Started 5 4 4 9
Completed 5 4 4 9
Not Completed 0 0 0 0
Period Title: Completed Follow for 1 Year
Started [1] 7 4 6 11
Completed 1 1 4 5
Not Completed 6 3 2 6
Reason Not Completed
Death             6             3             1             4
Still in FU             0             0             1             2
[1]
Any patient that is treated with study drug goes into follow up after treatment discontinuation.
Arm/Group Title Cohort 1 - Temozolomide 150 mg/m2 and Pazopanib 400 mg Cohort -1 -Temozolomide 100 mg/m2 and Pazopanib 400 mg Cohort -2 - Temozolomide 75 mg/m2 and Pazopanib 400 mg Phase II -Temozolomide 75 mg/m2 and Pazopanib 400 mg Total
Hide Arm/Group Description

Temozolomide 150 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28

temozolomide: Given PO

pazopanib hydrochloride: Given PO

Temozolomide 100 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28

temozolomide: Given PO

pazopanib hydrochloride: Given PO

Temozolomide 75 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28

temozolomide: Given PO

pazopanib hydrochloride: Given PO

Temozolomide 75mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28

temozolomide: Given PO

pazopanib hydrochloride: Given PO

Total of all reporting groups
Overall Number of Baseline Participants 7 5 6 11 29
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 5 participants 6 participants 11 participants 29 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
7
 100.0%
3
  60.0%
6
 100.0%
9
  81.8%
25
  86.2%
>=65 years
0
   0.0%
2
  40.0%
0
   0.0%
2
  18.2%
4
  13.8%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 5 participants 6 participants 11 participants 29 participants
Female
3
  42.9%
2
  40.0%
2
  33.3%
6
  54.5%
13
  44.8%
Male
4
  57.1%
3
  60.0%
4
  66.7%
5
  45.5%
16
  55.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 5 participants 6 participants 11 participants 29 participants
Hispanic or Latino
1
  14.3%
0
   0.0%
0
   0.0%
1
   9.1%
2
   6.9%
Not Hispanic or Latino
6
  85.7%
5
 100.0%
6
 100.0%
9
  81.8%
26
  89.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1
   9.1%
1
   3.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 5 participants 6 participants 11 participants 29 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
1
   9.1%
1
   3.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
  14.3%
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.4%
White
6
  85.7%
5
 100.0%
6
 100.0%
10
  90.9%
27
  93.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 7 participants 5 participants 6 participants 11 participants 29 participants
7 5 6 11 29
1.Primary Outcome
Title Determine the Maximum Tolerated Dose (MTD) of Temozolomide and Pazopanib Combination in Patients With Advanced Pancreatic Neuroendocrine Tumor (PNET) in Phase I
Hide Description MTD and recommended phase II dose (RP2D) determination for the combination of temozolomide and pazopanib in patients with advanced PNET will be achieved using a standard "3+3" dose escalation/de-escalation design. After each 3 patients are enrolled into the study, further enrollment will be temporarily suspended until safety has been reviewed for the first 28 days of treatment to determine if dose limiting toxicities have been experienced by patients and if a further 3 patients should be enrolled at the current dose or dose escalation/de-escalation for the next 3 patients should occur.
Time Frame After 28 days (1 course of treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
1 patient in Cohort -1 was not evaluable for this endpoint due to inability to absorb oral medications secondary to bowel edema
Arm/Group Title Cohort 1/Cohort -1/Cohort -2 - Temozolomide and Pazopanib
Hide Arm/Group Description:

Temozolomide 75 - 150 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28

temozolomide: Given PO

pazopanib hydrochloride: Given PO

Overall Number of Participants Analyzed 17
Measure Type: Number
Unit of Measure: mg/m2 and mg
Temozolomide 75
Pazopanib 400
2.Primary Outcome
Title Overall Response Rate (ORR) in Patients With Advanced Neuroendocrine Tumors (PNET) Treated With Temozolomide and Pazopanib Combination Treatment at the RP2D in Phase II
Hide Description

Overall response rate will be determined by the number of patients who's best response as assessed by RECIST 1.1 is complete response (CR) and partial response (PR) in patients with PNET that are enrolled at the recommended phase II dose (RP2D) (PK cohort included).

CR= Disappearance of all target lesions PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Time Frame After two courses of treatment (8 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
1 patient was determined not to be evaluable for response in phase II
Arm/Group Title Phase II -Temozolomide 75 mg/m2 and Pazopanib 400 mg
Hide Arm/Group Description:

Temozolomide 75mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28

temozolomide: Given PO

pazopanib hydrochloride: Given PO

Overall Number of Participants Analyzed 10
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
3.Secondary Outcome
Title Number of Toxicity Events Noted in Patients Undergoing This Treatment.
Hide Description For Patients in Phase I: Symptoms and Lab Results will be reviewed with patients according to this schedule.
Time Frame Weekly during the first course of treatment (Every 28 days) and then Bi-Weekly thereafter as long as patients are on treatment
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Amount of Pazopanib in the Blood at Various Timepoints After Administration
Hide Description For the Six Patients in Phase I portion who are enrolled in the PK cohort: Blood will be drawn on Day 1 before beginning treatment and again at 10 minutes, 30 minutes, 1, 2, 3, 4, 6 and 8 hours after beginning treatment. On Day 2- 24 hours after the first dose from Day 1, and again 10 minutes, 30 minutes, 1, 2, 3, 4, 6 and 8 hours after taking the second dose. Day 3 - 24 hours after the second dose from Day 2.
Time Frame Multiple timepoints during Days 1-3 of course 1 (see description)
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Number of Years That Patients Survive Without Experiencing Disease Progression
Hide Description For Patients in Phase II Portion: The Length of time between when the patient begins treatment and when disease progression is first noted will be calculated.
Time Frame Baseline and after every 2 courses of treatment (8 weeks)
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Number of Years That Patients Survive After Undergoing Study Treatment
Hide Description For Patients in Phase II Portion: The Length of time between when the patient begins treatment and when and when the patient becomes deceased will be calculated.
Time Frame Baseline and after every 2 courses of treatment (8 weeks)
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Number of Patients Experiencing Response to Treatment or Stable Disease
Hide Description For Patients in Phase II Portion: The number of patients demonstrating the complete response, partial response or stable disease after 8 weeks of treatment will be calculated.
Time Frame After every 2 courses of treatment (8 weeks)
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Number of Months That Patients Maintain a Response to Treatment Until Disease Progression or Death
Hide Description For Patients in Phase II Portion: The time patients start receiving treatment until disease progression will be calculated.
Time Frame After every 2 courses of treatment (8 weeks)
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Determine the Relationship Between Tumor Blood Flow and Overall Response Rate
Hide Description For Patients in Phase II Portion: Patients will have a perfusion functional computed tomography (fCT) scan at baseline and after two courses of treatment.
Time Frame At Baseline and after two corurses of treatment (8 weeks)
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Amount of a Particular Tumor Biomarker in Blood as Correlated With Progression Free Survival
Hide Description For Patients in Phase II Portion: The level of expression of tissue methyl-guanine methytransferase (MGMT)will be measured in tissue from the diagnostic biopsy and these results will be correlated with response rate.
Time Frame Baseline and at Response assessment after two courses of treatment (8 weeks)
Outcome Measure Data Not Reported
Time Frame Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days
Adverse Event Reporting Description This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.
 
Arm/Group Title Cohort 1 - Temozolomide 150 mg/m2 and Pazopanib 400 mg Cohort -1 -Temozolomide 100 mg/m2 and Pazopanib 400 mg Cohort -2 - Temozolomide 75 mg/m2 and Pazopanib 400 mg Phase II -Temozolomide 75 mg/m2 and Pazopanib 400 mg
Hide Arm/Group Description

Temozolomide 150 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28

temozolomide: Given PO

pazopanib hydrochloride: Given PO

Temozolomide 100 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28

temozolomide: Given PO

pazopanib hydrochloride: Given PO

Temozolomide 75 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28

temozolomide: Given PO

pazopanib hydrochloride: Given PO

Temozolomide 75mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28

temozolomide: Given PO

pazopanib hydrochloride: Given PO

All-Cause Mortality
Cohort 1 - Temozolomide 150 mg/m2 and Pazopanib 400 mg Cohort -1 -Temozolomide 100 mg/m2 and Pazopanib 400 mg Cohort -2 - Temozolomide 75 mg/m2 and Pazopanib 400 mg Phase II -Temozolomide 75 mg/m2 and Pazopanib 400 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/7 (85.71%)      4/5 (80.00%)      1/6 (16.67%)      4/11 (36.36%)    
Hide Serious Adverse Events
Cohort 1 - Temozolomide 150 mg/m2 and Pazopanib 400 mg Cohort -1 -Temozolomide 100 mg/m2 and Pazopanib 400 mg Cohort -2 - Temozolomide 75 mg/m2 and Pazopanib 400 mg Phase II -Temozolomide 75 mg/m2 and Pazopanib 400 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/7 (42.86%)      3/5 (60.00%)      1/6 (16.67%)      1/11 (9.09%)    
Blood and lymphatic system disorders         
Splenic hemorrage  1  1/7 (14.29%)  1 0/5 (0.00%)  0/6 (0.00%)  0/11 (0.00%) 
Gastrointestinal disorders         
Upper Gastrointestinal hemorrhage  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/11 (9.09%)  1
General disorders         
Guillian-Barre Syndrome  1  1/7 (14.29%)  1 0/5 (0.00%)  0/6 (0.00%)  0/11 (0.00%) 
Infections and infestations         
Shingles  1  1/7 (14.29%)  1 0/5 (0.00%)  0/6 (0.00%)  0/11 (0.00%) 
Investigations         
AST and ALT increased  1  0/7 (0.00%)  1/5 (20.00%)  1 1/6 (16.67%)  1 0/11 (0.00%) 
Thrombocytopenia  1 [1]  1/7 (14.29%)  1 0/5 (0.00%)  0/6 (0.00%)  0/11 (0.00%) 
Metabolism and nutrition disorders         
Protein calorie malnutrition  1 [2]  0/7 (0.00%)  1/5 (20.00%)  1 0/6 (0.00%)  0/11 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
ACTH secreting tumor with cushings syndrome  1 [3]  0/7 (0.00%)  1/5 (20.00%)  2 0/6 (0.00%)  0/11 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Epistasis  1  1/7 (14.29%)  1 0/5 (0.00%)  0/6 (0.00%)  0/11 (0.00%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
[1]
Patient also with neutropenia and white blood cell decreased during this event
[2]
Patient also with diarrhea at the time
[3]
patient with hypokalemia and diarrhea during first event and thrombocytopenia and leukopenia during the second event
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cohort 1 - Temozolomide 150 mg/m2 and Pazopanib 400 mg Cohort -1 -Temozolomide 100 mg/m2 and Pazopanib 400 mg Cohort -2 - Temozolomide 75 mg/m2 and Pazopanib 400 mg Phase II -Temozolomide 75 mg/m2 and Pazopanib 400 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/7 (100.00%)      5/5 (100.00%)      6/6 (100.00%)      17/17 (100.00%)    
Blood and lymphatic system disorders         
Hemoglobin (anemia)  1  6/7 (85.71%)  4/5 (80.00%)  3/6 (50.00%)  6/17 (35.29%) 
Petechiae  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Red blood cells decreased  1  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/17 (0.00%) 
Cardiac disorders         
Sinus bradycardia  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Increased heart rate  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Chest pain  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Ear and labyrinth disorders         
Hearing impaired  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Endocrine disorders         
Hypothyroidism  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Hyperparathyroidism  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Eye disorders         
Blurred vision  1  1/7 (14.29%)  0/5 (0.00%)  2/6 (33.33%)  0/17 (0.00%) 
Flashing lights  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Scleral disorder  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Floaters  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Retinal detachment  1  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/17 (0.00%) 
Optic nerve disorder  1  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/17 (0.00%) 
Cataract  1  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/17 (0.00%) 
Visual changes  1  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/17 (0.00%) 
Decreased visual Acuity  1  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/17 (0.00%) 
Gastrointestinal disorders         
Abdominal pain  1  3/7 (42.86%)  0/5 (0.00%)  4/6 (66.67%)  5/17 (29.41%) 
Ascites  1  1/7 (14.29%)  1/5 (20.00%)  0/6 (0.00%)  0/17 (0.00%) 
Abdominal bloating  1  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  1/17 (5.88%) 
Abdominal distension  1  1/7 (14.29%)  0/5 (0.00%)  1/6 (16.67%)  1/17 (5.88%) 
Constipation  1  3/7 (42.86%)  1/5 (20.00%)  3/6 (50.00%)  3/17 (17.65%) 
Diarrhea  1  5/7 (71.43%)  1/5 (20.00%)  5/6 (83.33%)  4/17 (23.53%) 
Dyspepsia  1  2/7 (28.57%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Gastroparesis  1  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/17 (0.00%) 
Flatulence  1  3/7 (42.86%)  2/5 (40.00%)  0/6 (0.00%)  1/17 (5.88%) 
Mucositis/stomatitis  1  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  1/17 (5.88%) 
Steatorrhea  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Nausea  1  7/7 (100.00%)  2/5 (40.00%)  5/6 (83.33%)  4/17 (23.53%) 
Oral pain  1  2/7 (28.57%)  1/5 (20.00%)  0/6 (0.00%)  1/17 (5.88%) 
Gastroesophageal reflux disease  1  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  3/17 (17.65%) 
Gastrointestinal pain  1  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  0/17 (0.00%) 
Vomiting  1  7/7 (100.00%)  1/5 (20.00%)  4/6 (66.67%)  2/17 (11.76%) 
Jaundice  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Abdominal swelling after eating  1  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  0/17 (0.00%) 
Dysphagia (difficulty swallowing)  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Peristalsis  1  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/17 (0.00%) 
Ventral herniaexact  1  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/17 (0.00%) 
Hematochezia  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
General disorders         
Chills  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Edema limbs  1  1/7 (14.29%)  1/5 (20.00%)  3/6 (50.00%)  3/17 (17.65%) 
Fatigue  1  5/7 (71.43%)  3/5 (60.00%)  4/6 (66.67%)  4/17 (23.53%) 
Fever  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Injection site reaction  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Irritability  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Non-cardiac chest pain  1  3/7 (42.86%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Pain  1  3/7 (42.86%)  0/5 (0.00%)  1/6 (16.67%)  1/17 (5.88%) 
Night sweats  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Flu like symptoms  1  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/17 (0.00%) 
Localized edema  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Infections and infestations         
Mucosal infection  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Pharyngitis  1  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/17 (0.00%) 
Tooth infection  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Upper respiratory infection  1  3/7 (42.86%)  0/5 (0.00%)  1/6 (16.67%)  0/17 (0.00%) 
Influenza  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Thrush (Candidiasis)  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Herpes zoster  1  2/7 (28.57%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Injury, poisoning and procedural complications         
Bruising  1  1/7 (14.29%)  0/5 (0.00%)  2/6 (33.33%)  0/17 (0.00%) 
Wound complication  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Right sided bicep tear  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Investigations         
Alkaline phosphatase  1  4/7 (57.14%)  3/5 (60.00%)  2/6 (33.33%)  5/17 (29.41%) 
ALT, SGPT (serum glutamic pyruvic transaminase) atinine  1  6/7 (85.71%)  4/5 (80.00%)  6/6 (100.00%)  7/17 (41.18%) 
AST, SGOT (serum glutamic oxaloacetic transaminase)  1  5/7 (71.43%)  4/5 (80.00%)  3/6 (50.00%)  10/17 (58.82%) 
Bilirubin (hyperbilirubinemia)  1  4/7 (57.14%)  2/5 (40.00%)  0/6 (0.00%)  0/17 (0.00%) 
Cholesterol high  1  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  0/17 (0.00%) 
Creatinine increased  1  1/7 (14.29%)  0/5 (0.00%)  2/6 (33.33%)  3/17 (17.65%) 
GGT increased  1  1/7 (14.29%)  1/5 (20.00%)  0/6 (0.00%)  0/17 (0.00%) 
INR increased  1  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  0/17 (0.00%) 
Lipase increased  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Lymphocyte count decreased  1  5/7 (71.43%)  2/5 (40.00%)  4/6 (66.67%)  7/17 (41.18%) 
Lymphocyte count increased  1  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  1/17 (5.88%) 
Neutrophil count decreased  1  5/7 (71.43%)  2/5 (40.00%)  3/6 (50.00%)  5/17 (29.41%) 
Platelet count decreased  1  5/7 (71.43%)  2/5 (40.00%)  3/6 (50.00%)  6/17 (35.29%) 
Weight loss  1  1/7 (14.29%)  2/5 (40.00%)  0/6 (0.00%)  3/17 (17.65%) 
White blood cell decreased  1  6/7 (85.71%)  2/5 (40.00%)  4/6 (66.67%)  4/17 (23.53%) 
Pneumatosis  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Metabolism and nutrition disorders         
Anorexia  1  4/7 (57.14%)  0/5 (0.00%)  2/6 (33.33%)  3/17 (17.65%) 
Dehydration  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Albumin, serum-low (hypoalbuminemia)  1  2/7 (28.57%)  3/5 (60.00%)  1/6 (16.67%)  2/17 (11.76%) 
Calcium, serum-high (hypercalcemia)  1  1/7 (14.29%)  0/5 (0.00%)  2/6 (33.33%)  2/17 (11.76%) 
Calcium, serum-low (hypocalcemia)  1  2/7 (28.57%)  1/5 (20.00%)  2/6 (33.33%)  2/17 (11.76%) 
Glucose intolerance  1  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  0/17 (0.00%) 
Glucose, serum-high (hyperglycemia)  1  4/7 (57.14%)  5/5 (100.00%)  5/6 (83.33%)  10/17 (58.82%) 
Glucose, serum-low(hypoglycemia)  1  0/7 (0.00%)  1/5 (20.00%)  1/6 (16.67%)  3/17 (17.65%) 
Magnesium, serum-high (hypermagnesemia)  1  1/7 (14.29%)  1/5 (20.00%)  0/6 (0.00%)  0/17 (0.00%) 
Magnesium, serum-low(hypomagnesemia)  1  1/7 (14.29%)  2/5 (40.00%)  1/6 (16.67%)  3/17 (17.65%) 
Phosphate, serum-low (hypophosphatemia)  1  2/7 (28.57%)  1/5 (20.00%)  4/6 (66.67%)  3/17 (17.65%) 
Potassium, serum-high(hyperkalemia)  1  1/7 (14.29%)  0/5 (0.00%)  2/6 (33.33%)  5/17 (29.41%) 
Potassium, serum-low(hypokalemia)  1  2/7 (28.57%)  4/5 (80.00%)  0/6 (0.00%)  2/17 (11.76%) 
Sodium, serum-high(hypernatremia)  1  1/7 (14.29%)  1/5 (20.00%)  1/6 (16.67%)  0/17 (0.00%) 
Sodium, serum-low(hyponatremia)  1  5/7 (71.43%)  4/5 (80.00%)  3/6 (50.00%)  3/17 (17.65%) 
Vitamin D deficiency  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Proteincalorie malnutrition  1  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  0/17 (0.00%) 
Low BUN  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Low chloride  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
High chloride  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Low serum protein  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Musculoskeletal and connective tissue disorders         
Intermittent mild cramping hands/feet  1  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  0/17 (0.00%) 
Arthralgia  1  2/7 (28.57%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Leg cramps at night  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Chest wall pain  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
generalized muscle weakness  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
pain in extremity  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  2/17 (11.76%) 
Osteoporosis  1  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/17 (0.00%) 
Back pain  1  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  2/17 (11.76%) 
Muscle weakness left-sided  1  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/17 (0.00%) 
Myalgia  1  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  1/17 (5.88%) 
Muscle cramps  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Right maxilla met biopsied  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Nervous system disorders         
Dizziness  1  5/7 (71.43%)  0/5 (0.00%)  2/6 (33.33%)  2/17 (11.76%) 
Dysgeusia  1  2/7 (28.57%)  1/5 (20.00%)  4/6 (66.67%)  1/17 (5.88%) 
Headache  1  6/7 (85.71%)  1/5 (20.00%)  2/6 (33.33%)  4/17 (23.53%) 
Peripheral sensory neuropathy  1  2/7 (28.57%)  0/5 (0.00%)  1/6 (16.67%)  0/17 (0.00%) 
Presyncope  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Tremor  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Anisocoria  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Attention deficit disorder  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Depressed level of consciousness  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Psychiatric disorders         
Insomnia  1  1/7 (14.29%)  0/5 (0.00%)  2/6 (33.33%)  1/17 (5.88%) 
Anxiety  1  2/7 (28.57%)  1/5 (20.00%)  2/6 (33.33%)  1/17 (5.88%) 
Depression  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Renal and urinary disorders         
Urinary burning  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Hematuria  1  1/7 (14.29%)  1/5 (20.00%)  0/6 (0.00%)  0/17 (0.00%) 
Proteinuria  1  2/7 (28.57%)  1/5 (20.00%)  0/6 (0.00%)  1/17 (5.88%) 
Nocturia  1  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  1/17 (5.88%) 
Urine discoloration  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Urine frequency  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  2/7 (28.57%)  0/5 (0.00%)  1/6 (16.67%)  0/17 (0.00%) 
Dyspnea  1  4/7 (57.14%)  0/5 (0.00%)  2/6 (33.33%)  0/17 (0.00%) 
Epistaxis  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Hoarseness  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Nasal congestion  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Sinus disorder  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Nasal discomfort  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Wheezing  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Voice alteration  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Hiccups  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Skin and subcutaneous tissue disorders         
Rash maculo-papular  1  2/7 (28.57%)  0/5 (0.00%)  2/6 (33.33%)  0/17 (0.00%) 
Rash acneiform  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Alopecia  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Skin hypopigmentation  1  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Pruritus  1  1/7 (14.29%)  0/5 (0.00%)  1/6 (16.67%)  0/17 (0.00%) 
Poison ivy rash  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Hair color changes  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  1/17 (5.88%) 
Precancerous lesion on lip/face  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Skin discoloration post shingles  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Petechial rash on breasts  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Ulceration on lower lip  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Hair color lightening  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Excoriations anterior lower extremities  1  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Dry skin  1  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/17 (0.00%) 
Hyperhidrosis  1  0/7 (0.00%)  0/5 (0.00%)  2/6 (33.33%)  0/17 (0.00%) 
Ecchymosis  1  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/17 (0.00%) 
Urticaria  1  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/17 (0.00%) 
Vascular disorders         
Hot flashes  1  2/7 (28.57%)  0/5 (0.00%)  0/6 (0.00%)  0/17 (0.00%) 
Hypertension  1  3/7 (42.86%)  2/5 (40.00%)  1/6 (16.67%)  1/17 (5.88%) 
Flushing  1  1/7 (14.29%)  0/5 (0.00%)  1/6 (16.67%)  0/17 (0.00%) 
Thromboembolic event  1  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  0/17 (0.00%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
On review of the phase II data it was determined that the study did not meet continuation criteria according to Simon II stage design and would not meet criteria even with the remaining slot filled. The study was closed to further accrual.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Sheetal Kircher, MD
Organization: Northwestern University
Phone: 312-695-0990
EMail: sheetal.kircher@nm.org
Layout table for additonal information
Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT01465659    
Other Study ID Numbers: NU 11I03
NCI-2011-02939 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
STU00053541 ( Other Identifier: Northwestern University IRB )
First Submitted: October 4, 2011
First Posted: November 6, 2011
Results First Submitted: May 12, 2020
Results First Posted: June 17, 2020
Last Update Posted: June 17, 2020