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Trial record 21 of 78 for:    vismodegib

Vismodegib in Treating Younger Patients With Recurrent or Refractory Medulloblastoma

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ClinicalTrials.gov Identifier: NCT01239316
Recruitment Status : Completed
First Posted : November 11, 2010
Results First Posted : January 14, 2016
Last Update Posted : January 14, 2016
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Recurrent Childhood Medulloblastoma
Interventions Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Drug: Vismodegib
Enrollment 12
Recruitment Details This study was distributed to the sites on 11/22/2010, and received the first IRB approval on 02/02/2011. It was closed to accrual on 03/25/2015. As of the closure date, 42 patients have been pre-screened for Hh pathway activation. Of the 42 patients, 9 patients with Hg pathway activated tumors were registered.
Pre-assignment Details There were three patients treated at the MTD of GDC-0449 on PBTC-025 who had Hh pathway activated tumors and who met the eligibility criteria for PBTC-032. These three patients were included in the assessment of the primary objectives for PBTC-032.
Arm/Group Title Hh Pathway Activated
Hide Arm/Group Description Pediatric patients with recurrent or refractory medulloblastoma with evidence of activation of Hedgehog (Hh) signaling pathway in their tumors.
Period Title: Overall Study
Started 12
Completed 0
Not Completed 12
Reason Not Completed
Progression/Relapse             11
Adverse Event             1
Arm/Group Title Hh Pathway Activated
Hide Arm/Group Description Pediatric patients with recurrent or refractory medulloblastoma with evidence of activation of Hedgehog (Hh) signaling pathway in their tumors.
Overall Number of Baseline Participants 12
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Median (Full Range)
Unit of measure:  Years
Number Analyzed 12 participants
10.4
(3.9 to 20.0)
[1]
Measure Description: Age at study enrollment
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants
Female
6
  50.0%
Male
6
  50.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants
Hispanic or Latino
2
  16.7%
Not Hispanic or Latino
8
  66.7%
Unknown or Not Reported
2
  16.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants
American Indian or Alaska Native
1
   8.3%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
8
  66.7%
More than one race
1
   8.3%
Unknown or Not Reported
2
  16.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 12 participants
12
1.Primary Outcome
Title Objective Response (CR+PR) Sustained for ≥ 8 Weeks
Hide Description Objective response is either a complete response or a partial response sustained for 8 weeks in a patient. The objective response rate will be reported separately for patients of each stratum. CR is complete disappearance of all enhancing tumor. PR is >= 50% reduction in tumor size.
Time Frame Up to 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Hh Pathway Activated
Hide Arm/Group Description:
Pediatric patients with recurrent or refractory medulloblastoma with evidence of activation of Hedgehog (Hh) signaling pathway in their tumors.
Overall Number of Participants Analyzed 12
Measure Type: Number
Unit of Measure: participants
1
2.Primary Outcome
Title Pharmacokinetics (Plasma) of GDC-0449
Hide Description plasma GDC-0449 concentration of day 21 in first course
Time Frame up to 12 month
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who have day 21 plasma GDC-0449 concentration data available
Arm/Group Title Hh Pathway Activated
Hide Arm/Group Description:
Pediatric patients with recurrent or refractory medulloblastoma with evidence of activation of Hedgehog (Hh) signaling pathway in their tumors.
Overall Number of Participants Analyzed 11
Median (Full Range)
Unit of Measure: uM
18
(9.5 to 45.3)
3.Secondary Outcome
Title Progression-free Survival
Hide Description Progression-free survival (PFS) is measured from the date of initial treatment with GDC-0449 until the earliest of progression or death on study. PFS is censored at the last tumor assessment date for patients without disease progression who have not died within 30 days of last exposure to study treatment. Kaplan-Meier method is used to estimate the progression-free survival.
Time Frame From start of treatment up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Hh Pathway Activated
Hide Arm/Group Description:
Pediatric patients with recurrent or refractory medulloblastoma with evidence of activation of Hedgehog (Hh) signaling pathway in their tumors.
Overall Number of Participants Analyzed 12
Median (95% Confidence Interval)
Unit of Measure: months
1.41
(0.69 to 3.68)
4.Secondary Outcome
Title Duration of Objective Response
Hide Description The duration of objective response is measured from the initial scan documenting complete or partial response that was subsequently confirmed until the earlier of documented progression or death on study. Duration of objective response is censored at the last tumor assessment date for patients without disease progression who have not died within 30 days of last exposure to study treatment.
Time Frame From start of treatment up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Patient with sustained objective response
Arm/Group Title Hh Pathway Activated
Hide Arm/Group Description:
Pediatric patients with recurrent or refractory medulloblastoma with evidence of activation of Hedgehog (Hh) signaling pathway in their tumors.
Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: months
2.83
5.Secondary Outcome
Title Pharmacokinetic Parameters of Vismodegib, CSF Penetration
Hide Description The estimated median of cerebrospinal fluid (CSF) drug penetration is reported when expressed as an AUC ratio of CSF vismodegib to that of unbound drug in plasma.
Time Frame up to 12 month
Hide Outcome Measure Data
Hide Analysis Population Description
The calculation of drug penetration is based on patients who had the course 1 plasma and CSF drug concentration data
Arm/Group Title Hh Pathway Activated
Hide Arm/Group Description:
Pediatric patients with recurrent or refractory medulloblastoma with evidence of activation of Hedgehog (Hh) signaling pathway in their tumors.
Overall Number of Participants Analyzed 11
Median (Full Range)
Unit of Measure: penetration rate
0.14
(0.07 to 0.28)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Hh Pathway Activated
Hide Arm/Group Description Pediatric patients with recurrent or refractory medulloblastoma with evidence of activation of Hedgehog (Hh) signaling pathway in their tumors.
All-Cause Mortality
Hh Pathway Activated
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Hh Pathway Activated
Affected / at Risk (%) # Events
Total   4/12 (33.33%)    
Gastrointestinal disorders   
Nausea  1  1/12 (8.33%)  1
Investigations   
Lymphocyte count decreased  1  3/12 (25.00%)  3
Platelet count decreased  1  1/12 (8.33%)  1
Musculoskeletal and connective tissue disorders   
Back pain  1  1/12 (8.33%)  1
Neck pain  1  1/12 (8.33%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Hh Pathway Activated
Affected / at Risk (%) # Events
Total   12/12 (100.00%)    
Blood and lymphatic system disorders   
Anemia  1  3/12 (25.00%)  4
Eye disorders   
Blurred vision  1  1/12 (8.33%)  1
Gastrointestinal disorders   
Abdominal pain  1  1/12 (8.33%)  1
Constipation  1  2/12 (16.67%)  3
Diarrhea  1  3/12 (25.00%)  3
Lip pain  1  1/12 (8.33%)  1
Nausea  1  4/12 (33.33%)  4
Stomach pain  1  1/12 (8.33%)  1
Vomiting  1  6/12 (50.00%)  6
General disorders   
Death NOS  1  2/12 (16.67%)  2
Fatigue  1  6/12 (50.00%)  6
Gait disturbance  1  1/12 (8.33%)  1
Pain  1  1/12 (8.33%)  1
Investigations   
Alanine aminotransferase increased  1  6/12 (50.00%)  8
Aspartate aminotransferase increased  1  3/12 (25.00%)  3
Lymphocyte count decreased  1  2/12 (16.67%)  4
Neutrophil count decreased  1  1/12 (8.33%)  1
Platelet count decreased  1  1/12 (8.33%)  1
Weight loss  1  1/12 (8.33%)  1
White blood cell decreased  1  2/12 (16.67%)  2
Metabolism and nutrition disorders   
Anorexia  1  2/12 (16.67%)  2
Dehydration  1  1/12 (8.33%)  1
Hyperglycemia  1  2/12 (16.67%)  3
Hypoalbuminemia  1  2/12 (16.67%)  3
Hypocalcemia  1  1/12 (8.33%)  1
Hypoglycemia  1  1/12 (8.33%)  1
Hypokalemia  1  2/12 (16.67%)  4
Hypomagnesemia  1  4/12 (33.33%)  4
Hyponatremia  1  1/12 (8.33%)  1
Hypophosphatemia  1  2/12 (16.67%)  2
Musculoskeletal and connective tissue disorders   
Musculoskeletal and connective tissue disorder - Other (Specify, __)[mild cramping in hands.]  1  1/12 (8.33%)  1
Musculoskeletal and connective tissue disorder - Other (Specify, __)[muscle cramps in calf]  1  1/12 (8.33%)  1
Musculoskeletal and connective tissue disorder - Other (Specify, __)[Muscle Cramps.]  1  1/12 (8.33%)  1
Arthralgia  1  3/12 (25.00%)  3
Back pain  1  2/12 (16.67%)  2
Bone pain  1  1/12 (8.33%)  2
Muscle weakness lower limb  1  1/12 (8.33%)  1
Musculoskeletal and connective tissue disorder - Other specify[Generalized muscle aches]  1  1/12 (8.33%)  1
Musculoskeletal and connective tissue disorder - Other, specify[Leg muscle cramps]  1  1/12 (8.33%)  1
Musculoskeletal and connective tissue disorder - Other, specify[Muscle spasm/twitching]  1  1/12 (8.33%)  1
Musculoskeletal and connective tissue disorder - Other, specify[MUSCLE SPASMS/TWITCHING]  1  1/12 (8.33%)  1
Musculoskeletal and connective tissue disorder - Other, specify[muscle twitching]  1  1/12 (8.33%)  1
Myalgia  1  1/12 (8.33%)  1
Neck pain  1  1/12 (8.33%)  2
Pain in extremity  1  3/12 (25.00%)  3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify  1  2/12 (16.67%)  2
Nervous system disorders   
Depressed level of consciousness  1  1/12 (8.33%)  1
Dizziness  1  1/12 (8.33%)  1
Dysarthria  1  2/12 (16.67%)  2
Dysgeusia  1  2/12 (16.67%)  2
Headache  1  4/12 (33.33%)  4
Hydrocephalus  1  1/12 (8.33%)  1
Movements involuntary  1  1/12 (8.33%)  1
Paresthesia  1  1/12 (8.33%)  2
Psychiatric disorders   
Anxiety  1  1/12 (8.33%)  1
Respiratory, thoracic and mediastinal disorders   
Allergic rhinitis  1  1/12 (8.33%)  1
Cough  1  4/12 (33.33%)  5
Epistaxis  1  1/12 (8.33%)  1
Nasal congestion  1  2/12 (16.67%)  2
Respiratory, thoracic and mediastinal disorders - Other, specify  1  1/12 (8.33%)  1
Sore throat  1  1/12 (8.33%)  1
Skin and subcutaneous tissue disorders   
Alopecia  1  1/12 (8.33%)  1
Hyperhidrosis  1  1/12 (8.33%)  1
Purpura  1  1/12 (8.33%)  1
Rash acneiform  1  1/12 (8.33%)  1
Skin hypopigmentation  1  1/12 (8.33%)  1
Vascular disorders   
Hot flashes  1  1/12 (8.33%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
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: Tong Lin (Biostatistician)
Organization: St. Jude Children's Research Hospital
Phone: 9015952048
EMail: Tong.Lin@stjude.org
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01239316     History of Changes
Other Study ID Numbers: NCI-2011-02546
NCI-2011-02546 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000688451
PBTC-032
PBTC-032 ( Other Identifier: Pediatric Brain Tumor Consortium )
PBTC-032 ( Other Identifier: CTEP )
U01CA081457 ( U.S. NIH Grant/Contract )
First Submitted: November 10, 2010
First Posted: November 11, 2010
Results First Submitted: December 10, 2015
Results First Posted: January 14, 2016
Last Update Posted: January 14, 2016