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17AAG to Treat Kidney Tumors in Von Hippel-Lindau Disease

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ClinicalTrials.gov Identifier: NCT00088374
Recruitment Status : Completed
First Posted : July 26, 2004
Results First Posted : September 29, 2011
Last Update Posted : July 27, 2012
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Hippel-Lindau Disease
Kidney Cancer
Interventions Drug: 17 allylamino-17-demethoxygeldanamycin
Drug: 18 FDG (Fludeoxyglucose 18F)
Drug: [15-O] H2O
Drug: EPL diluent
Enrollment 9
Recruitment Details The accrual ceiling for this study is 25 patients. With an expected accrual of 10-12 patients per year, we expect to complete the accrual within 2-3 years.
Pre-assignment Details  
Arm/Group Title VHL Associated Renal Tumors
Hide Arm/Group Description 17-AAG intravenous infusions at a dose of 300 mg/m2 into a vein once a week for 3 weeks out of every 4, for 3 months; on days 1, 8, and 15 of 28 cycles. The infusions last up to 1 to 2 hours.
Period Title: Overall Study
Started 9
Completed 7
Not Completed 2
Reason Not Completed
patient did not receive any 17AAG             1
patient received <1 cycle only of 17AAG             1
Arm/Group Title VHL Associated Renal Tumors
Hide Arm/Group Description 17-AAG intravenous infusions at a dose of 300 mg/m2 into a vein once a week for 3 weeks out of every 4, for 3 months; on days 1, 8, and 15 of 28 cycles. The infusions last up to 1 to 2 hours.
Overall Number of Baseline Participants 9
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants
<=18 years
0
   0.0%
Between 18 and 65 years
8
  88.9%
>=65 years
1
  11.1%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9 participants
48.32  (10.82)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants
Female
3
  33.3%
Male
6
  66.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 9 participants
9
1.Primary Outcome
Title Number of Participants With a Renal Tumor Response
Hide Description Response is defined as the number of patients who experience a disease response (complete response (CR) or partial response (PR) of renal tumors)per RECIST criteria. CR is the disappearance of all target lesions. PR is at least a 20% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. See the protocol Link module for the full criteria if desired.
Time Frame 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
8 patients were evaluable (received at least one dose of drug and had a follow up scan).
Arm/Group Title Participants With VHL Associated Renal Tumors
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 8
Measure Type: Number
Unit of Measure: participants
0
2.Secondary Outcome
Title Number of Participants With a Non-renal Tumor Response
Hide Description Number of patients who have a PR or CR of non-renal lesions (pancreatic tumors, pheochromocytomas, and hemangioblastomas). The effect of treatment on the lesions will be evaluated at baseline and at the time of restaging (12 weeks) per RECIST criteria. RECIST is defined as changes in only the largest diameter (unidimensional measurement) of the tumor lesions. Lesions are either measurable or non-measurable using the criteria. See the protocol Link module for the full criteria if desired.
Time Frame Baseline and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
There were only two patients with measurable nonrenal tumors and hence the number of participants analyzed is correct.
Arm/Group Title Participants With VHL Associated Renal Tumors
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 2
Measure Type: Number
Unit of Measure: participants
0
3.Secondary Outcome
Title The Number of Participants With Adverse Events
Hide Description

Here are the total number of participants with adverse events. For the detailed list of adverse events see the adverse event module.

The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for adverse event reporting. For a detailed description see the link in the Protocol Link module.

Time Frame 1 yr, 364 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Participants With VHL Associated Renal Tumors
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 9
Measure Type: Number
Unit of Measure: participants
9
4.Secondary Outcome
Title The Number of Participants With HIF, HSP90, and HSP70 Modulation in Resected Tumor Tissue and/or Peripheral Blood Lymphocytes
Hide Description Measurement of HIF, HSP90 and HSP70 levels by Western Blot in tumor tissue and/or lymphocytes to assess modulation of these biomarkers in response to 17 AAG treatment. Pretreatment tumor samples (when available) and resected tumors (in those patients who did not have a response and underwent surgical resection of their tumor) were to be used for this analysis. Levels of Hsp90, Hsp70, HIF and HIF transcriptional targets in resected tumor will be compared to respective levels in tumors previously resected from other VHL patients (not treated with 17AAG).
Time Frame Baseline and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This analysis was not performed as it was felt that there were not a sufficient number of samples to enable a meaningful analysis.
Arm/Group Title Participants With VHL Associated Renal Tumors
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Number of Patients in Whom Renal Tumors Could be Identified by Positron Emission Tomography (PET)Based on Fludeoxyglucose 18F (18FDG) Uptake
Hide Description Images were acquired after the intravenous administration of 18FDG and H2015 and used to analyze glucose uptake and estimate blood flow. The parameter to be measured is SUV (standard uptake value(s)) and/or mL/min/gm.
Time Frame Baseline and at 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Response was not the endpoint. The SUV values were in the 2-3 range and hence renal tumors could not be clearly identified by this technique in any of the patients.
Arm/Group Title Participants With VHL Associated Renal Tumors
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 5
Measure Type: Number
Unit of Measure: participants
0
6.Secondary Outcome
Title Number of Participants With Flow Dynamics Measured by DCE MRI Within the Renal and Non-renal Tumor
Hide Description Dynamic images will be acquired before and after the intravenous administration of 0.1 mmol/kg of Gadolinium Diethylene triamine pentaacetic acid (DTPA). Time activity curves will be generated over a period of ten minutes. The parameter to be measured is the forward contrast transfer rate (Ktrans), the reverse contrast transfer rate (Kep), and/or the extravascular extracellular space volume fraction (Ve). Flow dynamics are a measure of blood flow changes in the tumor and are determined using the parameters we had previously defined (Ktrans, Kep, etc.).
Time Frame Baseline and during therapy (12 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
It is not the magnitude of changes in Ktrans, Kep, and Ve that limit our abililty, but the fact that this data was available in only a small number of patients.
Arm/Group Title Participants With VHL Associated Renal Tumors
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 4
Measure Type: Number
Unit of Measure: participants with changes
3
Time Frame 2 years, 364 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Participants With VHL Associated Renal Tumors
Hide Arm/Group Description [Not Specified]
All-Cause Mortality
Participants With VHL Associated Renal Tumors
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Participants With VHL Associated Renal Tumors
Affected / at Risk (%) # Events
Total   1/9 (11.11%)    
Nervous system disorders   
Dizziness  1  1/9 (11.11%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA10/CTCAE (3.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Participants With VHL Associated Renal Tumors
Affected / at Risk (%) # Events
Total   8/9 (88.89%)    
Blood and lymphatic system disorders   
HEMORRHAGE/BLEEDING:: Hemorrhage, GI:: Oral cavity  1  1/9 (11.11%)  1
HEMORRHAGE/BLEEDING:: Hemorrhage, pulmonary/upper respiratory:: Nose  1  1/9 (11.11%)  1
Cardiac disorders   
CARDIAC ARRHYTHMIA:: Conduction abnormality/atrioventricular heart block:: AV Block-First degree  1  1/9 (11.11%)  5
CARDIAC ARRHYTHMIA:: Conduction abnormality/atrioventricular heart block:: AV Block-Second degree Mo  1  1/9 (11.11%)  1
CARDIAC ARRHYTHMIA:: Supraventricular and nodal arrhythmia:: Sinus bradycardia  1  3/9 (33.33%)  14
CARDIAC ARRHYTHMIA:: Supraventricular and nodal arrhythmia:: Sinus tachycardia  1  1/9 (11.11%)  1
CARDIAC ARRHYTHMIA:: Ventricular arrhythmia:: Ventricular tachycardia  1  1/9 (11.11%)  2
CARDIAC GENERAL:: Left ventricular diastolic dysfunction  1  1/9 (11.11%)  1
Congenital, familial and genetic disorders   
CARDIAC ARRHYTHMIA:: Palpitations  1  1/9 (11.11%)  1
Gastrointestinal disorders   
GASTROINTESTINAL:: Anorexia  1  1/9 (11.11%)  1
GASTROINTESTINAL:: Constipation  1  1/9 (11.11%)  1
GASTROINTESTINAL:: Diarrhea  1  2/9 (22.22%)  5
GASTROINTESTINAL:: Dysphagia (difficulty swallowing)  1  1/9 (11.11%)  1
GASTROINTESTINAL:: Heartburn/dyspepsia  1  1/9 (11.11%)  1
GASTROINTESTINAL:: Nausea  1  7/9 (77.78%)  25
GASTROINTESTINAL:: Salivary gland changes/saliva  1  1/9 (11.11%)  7
GASTROINTESTINAL:: Taste alteration (dysgeusia)  1  5/9 (55.56%)  16
GASTROINTESTINAL:: Vomiting  1  2/9 (22.22%)  2
General disorders   
CONSTITUTIONAL SYMPTOMS:: Fatigue (asthenia, lethargy, malaise)  1  5/9 (55.56%)  14
CONSTITUTIONAL SYMPTOMS:: Insomnia  1  2/9 (22.22%)  2
CONSTITUTIONAL SYMPTOMS:: Odor (patient odor)  1  1/9 (11.11%)  1
CONSTITUTIONAL SYMPTOMS:: Weight gain  1  1/9 (11.11%)  1
CONSTITUTIONAL SYMPTOMS:: Weight loss  1  1/9 (11.11%)  2
Investigations   
BLOOD/BONE MARROW:: Hemoglobin  1  1/9 (11.11%)  1
BLOOD/BONE MARROW:: Leukocytes (total WBC)  1  1/9 (11.11%)  2
BLOOD/BONE MARROW:: Lymphopenia  1  1/9 (11.11%)  2
Metabolism and nutrition disorders   
METABOLIC/LABORATORY:: ALT, SGPT (serum glutamic pyruvic transaminase)  1  1/9 (11.11%)  2
METABOLIC/LABORATORY:: AST, SGOT(serum glutamic oxaloacetic transaminase)  1  1/9 (11.11%)  2
METABOLIC/LABORATORY:: Albumin, serum-low (hypoalbuminemia)  1  3/9 (33.33%)  4
METABOLIC/LABORATORY:: Bilirubin (hyperbilirubinemia)  1  1/9 (11.11%)  1
METABOLIC/LABORATORY:: CPK (creatine phosphokinase)  1  2/9 (22.22%)  2
METABOLIC/LABORATORY:: Calcium, serum-high (hypercalcemia)  1  1/9 (11.11%)  1
METABOLIC/LABORATORY:: Calcium, serum-low (hypocalcemia)  1  2/9 (22.22%)  3
METABOLIC/LABORATORY:: Glucose, serum-high (hyperglycemia)  1  4/9 (44.44%)  7
METABOLIC/LABORATORY:: Glucose, serum-low (hypoglycemia)  1  1/9 (11.11%)  1
METABOLIC/LABORATORY:: Magnesium, serum-high (hypermagnesemia)  1  2/9 (22.22%)  5
METABOLIC/LABORATORY:: Metabolic/Laboratory - Other (Specify, __)  1 [1]  1/9 (11.11%)  1
METABOLIC/LABORATORY:: Phosphate, serum-low (hypophosphatemia)  1  2/9 (22.22%)  2
METABOLIC/LABORATORY:: Potassium, serum-high (hyperkalemia)  1  1/9 (11.11%)  1
METABOLIC/LABORATORY:: Potassium, serum-low (hypokalemia)  1  1/9 (11.11%)  2
METABOLIC/LABORATORY:: Sodium, serum-low (hyponatremia)  1  1/9 (11.11%)  2
METABOLIC/LABORATORY:: Uric acid, serum-high (hyperuricemia)  1  3/9 (33.33%)  4
Musculoskeletal and connective tissue disorders   
MUSCULOSKELETAL/SOFT TISSUE:: Extremity-upper (function)  1  1/9 (11.11%)  1
PAIN:: Pain:: Abdomen NOS  1  2/9 (22.22%)  8
PAIN:: Pain:: Back  1  1/9 (11.11%)  5
PAIN:: Pain:: Bone  1  1/9 (11.11%)  21
PAIN:: Pain:: Chest wall  1  1/9 (11.11%)  2
PAIN:: Pain:: Extremity-limb  1  1/9 (11.11%)  1
PAIN:: Pain:: Muscle  1  3/9 (33.33%)  4
PAIN:: Pain:: Neck  1  1/9 (11.11%)  5
PAIN:: Pain:: Pelvis  1  1/9 (11.11%)  4
Nervous system disorders   
NEUROLOGY:: Ataxia (incoordination)  1  1/9 (11.11%)  1
NEUROLOGY:: Cognitive disturbance  1  1/9 (11.11%)  1
NEUROLOGY:: Dizziness  1  5/9 (55.56%)  5
NEUROLOGY:: Neurology - Other (Specify, __)  1 [2]  1/9 (11.11%)  1
PAIN:: Pain:: Head/headache  1  5/9 (55.56%)  8
PAIN:: Pain:: Pain NOS  1  1/9 (11.11%)  1
Respiratory, thoracic and mediastinal disorders   
ALLERGY/IMMUNOLOGY:: Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)  1  3/9 (33.33%)  3
PULMONARY/UPPER RESPIRATORY:: Cough  1  3/9 (33.33%)  4
PULMONARY/UPPER RESPIRATORY:: Fistula, pulmonary/upper respiratory:: Lung  1  1/9 (11.11%)  1
PULMONARY/UPPER RESPIRATORY:: Pulmonary/Upper Respiratory - Other (Specify, __)  1 [3]  1/9 (11.11%)  1
Skin and subcutaneous tissue disorders   
DERMATOLOGY/SKIN:: Rash/desquamation  1  1/9 (11.11%)  1
DERMATOLOGY/SKIN:: Rash: acne/acneiform  1  1/9 (11.11%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA10/CTCAE (3.0)
[1]
High LDH
[2]
Dizziness
[3]
nasal drying
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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
Name/Title: William M. Linehan, M.D.
Organization: National Cancer Institute, National Institutes of Health
Phone: 301-496-6353
Responsible Party: William M. Linehan, M.D., National Cancer Institute, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00088374     History of Changes
Obsolete Identifiers: NCT00089375
Other Study ID Numbers: 040238
04-C-0238 ( Other Identifier: Clinical Center (CC), National Institutes of Health (NIH) )
040238 ( Other Identifier: Clinical Center (CC), National Institutes of HEalth (NIH) )
First Submitted: July 23, 2004
First Posted: July 26, 2004
Results First Submitted: May 24, 2011
Results First Posted: September 29, 2011
Last Update Posted: July 27, 2012