Trial Outcomes & Findings for 17AAG to Treat Kidney Tumors in Von Hippel-Lindau Disease (NCT NCT00088374)
NCT ID: NCT00088374
Last Updated: 2012-07-27
Results Overview
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.
COMPLETED
PHASE2
9 participants
12 weeks
2012-07-27
Participant Flow
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.
Participant milestones
| Measure |
VHL Associated Renal Tumors
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 Study
STARTED
|
9
|
|
Overall Study
COMPLETED
|
7
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
VHL Associated Renal Tumors
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 Study
patient did not receive any 17AAG
|
1
|
|
Overall Study
patient received <1 cycle only of 17AAG
|
1
|
Baseline Characteristics
17AAG to Treat Kidney Tumors in Von Hippel-Lindau Disease
Baseline characteristics by cohort
| Measure |
VHL Associated Renal Tumors
n=9 Participants
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.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
8 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=93 Participants
|
|
Age Continuous
|
48.32 years
STANDARD_DEVIATION 10.82 • n=93 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
9 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: 8 patients were evaluable (received at least one dose of drug and had a follow up scan).
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.
Outcome measures
| Measure |
Participants With VHL Associated Renal Tumors
n=8 Participants
|
|---|---|
|
Number of Participants With a Renal Tumor Response
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline and 12 weeksPopulation: There were only two patients with measurable nonrenal tumors and hence the number of participants analyzed is correct.
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.
Outcome measures
| Measure |
Participants With VHL Associated Renal Tumors
n=2 Participants
|
|---|---|
|
Number of Participants With a Non-renal Tumor Response
|
0 participants
|
SECONDARY outcome
Timeframe: 1 yr, 364 daysHere 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.
Outcome measures
| Measure |
Participants With VHL Associated Renal Tumors
n=9 Participants
|
|---|---|
|
The Number of Participants With Adverse Events
|
9 participants
|
SECONDARY outcome
Timeframe: Baseline and 12 weeksPopulation: This analysis was not performed as it was felt that there were not a sufficient number of samples to enable a meaningful analysis.
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).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and at 12 weeksPopulation: 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.
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.
Outcome measures
| Measure |
Participants With VHL Associated Renal Tumors
n=5 Participants
|
|---|---|
|
Number of Patients in Whom Renal Tumors Could be Identified by Positron Emission Tomography (PET)Based on Fludeoxyglucose 18F (18FDG) Uptake
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline and during therapy (12 weeks)Population: 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.
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.).
Outcome measures
| Measure |
Participants With VHL Associated Renal Tumors
n=4 Participants
|
|---|---|
|
Number of Participants With Flow Dynamics Measured by DCE MRI Within the Renal and Non-renal Tumor
|
3 participants with changes
|
Adverse Events
Participants With VHL Associated Renal Tumors
Serious adverse events
| Measure |
Participants With VHL Associated Renal Tumors
n=9 participants at risk
|
|---|---|
|
Nervous system disorders
Dizziness
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
Other adverse events
| Measure |
Participants With VHL Associated Renal Tumors
n=9 participants at risk
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
ALLERGY/IMMUNOLOGY:: Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)
|
33.3%
3/9 • Number of events 3 • 2 years, 364 days
|
|
Investigations
BLOOD/BONE MARROW:: Hemoglobin
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Investigations
BLOOD/BONE MARROW:: Leukocytes (total WBC)
|
11.1%
1/9 • Number of events 2 • 2 years, 364 days
|
|
Investigations
BLOOD/BONE MARROW:: Lymphopenia
|
11.1%
1/9 • Number of events 2 • 2 years, 364 days
|
|
Cardiac disorders
CARDIAC ARRHYTHMIA:: Conduction abnormality/atrioventricular heart block:: AV Block-First degree
|
11.1%
1/9 • Number of events 5 • 2 years, 364 days
|
|
Cardiac disorders
CARDIAC ARRHYTHMIA:: Conduction abnormality/atrioventricular heart block:: AV Block-Second degree Mo
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Congenital, familial and genetic disorders
CARDIAC ARRHYTHMIA:: Palpitations
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Cardiac disorders
CARDIAC ARRHYTHMIA:: Supraventricular and nodal arrhythmia:: Sinus bradycardia
|
33.3%
3/9 • Number of events 14 • 2 years, 364 days
|
|
Cardiac disorders
CARDIAC ARRHYTHMIA:: Supraventricular and nodal arrhythmia:: Sinus tachycardia
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Cardiac disorders
CARDIAC ARRHYTHMIA:: Ventricular arrhythmia:: Ventricular tachycardia
|
11.1%
1/9 • Number of events 2 • 2 years, 364 days
|
|
Cardiac disorders
CARDIAC GENERAL:: Left ventricular diastolic dysfunction
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
General disorders
CONSTITUTIONAL SYMPTOMS:: Fatigue (asthenia, lethargy, malaise)
|
55.6%
5/9 • Number of events 14 • 2 years, 364 days
|
|
General disorders
CONSTITUTIONAL SYMPTOMS:: Insomnia
|
22.2%
2/9 • Number of events 2 • 2 years, 364 days
|
|
General disorders
CONSTITUTIONAL SYMPTOMS:: Odor (patient odor)
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
General disorders
CONSTITUTIONAL SYMPTOMS:: Weight gain
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
General disorders
CONSTITUTIONAL SYMPTOMS:: Weight loss
|
11.1%
1/9 • Number of events 2 • 2 years, 364 days
|
|
Skin and subcutaneous tissue disorders
DERMATOLOGY/SKIN:: Rash/desquamation
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Skin and subcutaneous tissue disorders
DERMATOLOGY/SKIN:: Rash: acne/acneiform
|
11.1%
1/9 • Number of events 2 • 2 years, 364 days
|
|
Gastrointestinal disorders
GASTROINTESTINAL:: Anorexia
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Gastrointestinal disorders
GASTROINTESTINAL:: Constipation
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Gastrointestinal disorders
GASTROINTESTINAL:: Diarrhea
|
22.2%
2/9 • Number of events 5 • 2 years, 364 days
|
|
Gastrointestinal disorders
GASTROINTESTINAL:: Dysphagia (difficulty swallowing)
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Gastrointestinal disorders
GASTROINTESTINAL:: Heartburn/dyspepsia
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Gastrointestinal disorders
GASTROINTESTINAL:: Nausea
|
77.8%
7/9 • Number of events 25 • 2 years, 364 days
|
|
Gastrointestinal disorders
GASTROINTESTINAL:: Salivary gland changes/saliva
|
11.1%
1/9 • Number of events 7 • 2 years, 364 days
|
|
Gastrointestinal disorders
GASTROINTESTINAL:: Taste alteration (dysgeusia)
|
55.6%
5/9 • Number of events 16 • 2 years, 364 days
|
|
Gastrointestinal disorders
GASTROINTESTINAL:: Vomiting
|
22.2%
2/9 • Number of events 2 • 2 years, 364 days
|
|
Blood and lymphatic system disorders
HEMORRHAGE/BLEEDING:: Hemorrhage, GI:: Oral cavity
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Blood and lymphatic system disorders
HEMORRHAGE/BLEEDING:: Hemorrhage, pulmonary/upper respiratory:: Nose
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Metabolism and nutrition disorders
METABOLIC/LABORATORY:: ALT, SGPT (serum glutamic pyruvic transaminase)
|
11.1%
1/9 • Number of events 2 • 2 years, 364 days
|
|
Metabolism and nutrition disorders
METABOLIC/LABORATORY:: AST, SGOT(serum glutamic oxaloacetic transaminase)
|
11.1%
1/9 • Number of events 2 • 2 years, 364 days
|
|
Metabolism and nutrition disorders
METABOLIC/LABORATORY:: Albumin, serum-low (hypoalbuminemia)
|
33.3%
3/9 • Number of events 4 • 2 years, 364 days
|
|
Metabolism and nutrition disorders
METABOLIC/LABORATORY:: Bilirubin (hyperbilirubinemia)
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Metabolism and nutrition disorders
METABOLIC/LABORATORY:: CPK (creatine phosphokinase)
|
22.2%
2/9 • Number of events 2 • 2 years, 364 days
|
|
Metabolism and nutrition disorders
METABOLIC/LABORATORY:: Calcium, serum-high (hypercalcemia)
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Metabolism and nutrition disorders
METABOLIC/LABORATORY:: Calcium, serum-low (hypocalcemia)
|
22.2%
2/9 • Number of events 3 • 2 years, 364 days
|
|
Metabolism and nutrition disorders
METABOLIC/LABORATORY:: Glucose, serum-high (hyperglycemia)
|
44.4%
4/9 • Number of events 7 • 2 years, 364 days
|
|
Metabolism and nutrition disorders
METABOLIC/LABORATORY:: Glucose, serum-low (hypoglycemia)
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Metabolism and nutrition disorders
METABOLIC/LABORATORY:: Magnesium, serum-high (hypermagnesemia)
|
22.2%
2/9 • Number of events 5 • 2 years, 364 days
|
|
Metabolism and nutrition disorders
METABOLIC/LABORATORY:: Metabolic/Laboratory - Other (Specify, __)
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Metabolism and nutrition disorders
METABOLIC/LABORATORY:: Phosphate, serum-low (hypophosphatemia)
|
22.2%
2/9 • Number of events 2 • 2 years, 364 days
|
|
Metabolism and nutrition disorders
METABOLIC/LABORATORY:: Potassium, serum-high (hyperkalemia)
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Metabolism and nutrition disorders
METABOLIC/LABORATORY:: Potassium, serum-low (hypokalemia)
|
11.1%
1/9 • Number of events 2 • 2 years, 364 days
|
|
Metabolism and nutrition disorders
METABOLIC/LABORATORY:: Sodium, serum-low (hyponatremia)
|
11.1%
1/9 • Number of events 2 • 2 years, 364 days
|
|
Metabolism and nutrition disorders
METABOLIC/LABORATORY:: Uric acid, serum-high (hyperuricemia)
|
33.3%
3/9 • Number of events 4 • 2 years, 364 days
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL/SOFT TISSUE:: Extremity-upper (function)
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Nervous system disorders
NEUROLOGY:: Ataxia (incoordination)
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Nervous system disorders
NEUROLOGY:: Cognitive disturbance
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Nervous system disorders
NEUROLOGY:: Dizziness
|
55.6%
5/9 • Number of events 5 • 2 years, 364 days
|
|
Nervous system disorders
NEUROLOGY:: Neurology - Other (Specify, __)
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Musculoskeletal and connective tissue disorders
PAIN:: Pain:: Abdomen NOS
|
22.2%
2/9 • Number of events 8 • 2 years, 364 days
|
|
Musculoskeletal and connective tissue disorders
PAIN:: Pain:: Back
|
11.1%
1/9 • Number of events 5 • 2 years, 364 days
|
|
Musculoskeletal and connective tissue disorders
PAIN:: Pain:: Bone
|
11.1%
1/9 • Number of events 21 • 2 years, 364 days
|
|
Musculoskeletal and connective tissue disorders
PAIN:: Pain:: Chest wall
|
11.1%
1/9 • Number of events 2 • 2 years, 364 days
|
|
Musculoskeletal and connective tissue disorders
PAIN:: Pain:: Extremity-limb
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Nervous system disorders
PAIN:: Pain:: Head/headache
|
55.6%
5/9 • Number of events 8 • 2 years, 364 days
|
|
Musculoskeletal and connective tissue disorders
PAIN:: Pain:: Muscle
|
33.3%
3/9 • Number of events 4 • 2 years, 364 days
|
|
Musculoskeletal and connective tissue disorders
PAIN:: Pain:: Neck
|
11.1%
1/9 • Number of events 5 • 2 years, 364 days
|
|
Nervous system disorders
PAIN:: Pain:: Pain NOS
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Musculoskeletal and connective tissue disorders
PAIN:: Pain:: Pelvis
|
11.1%
1/9 • Number of events 4 • 2 years, 364 days
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY/UPPER RESPIRATORY:: Cough
|
33.3%
3/9 • Number of events 4 • 2 years, 364 days
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY/UPPER RESPIRATORY:: Fistula, pulmonary/upper respiratory:: Lung
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY/UPPER RESPIRATORY:: Pulmonary/Upper Respiratory - Other (Specify, __)
|
11.1%
1/9 • Number of events 1 • 2 years, 364 days
|
Additional Information
William M. Linehan, M.D.
National Cancer Institute, National Institutes of Health
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place