Trial Outcomes & Findings for Vismodegib in Treating Younger Patients With Recurrent or Refractory Medulloblastoma (NCT NCT01239316)
NCT ID: NCT01239316
Last Updated: 2016-01-14
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
12 participants
Primary outcome timeframe
Up to 12 months
Results posted on
2016-01-14
Participant Flow
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.
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.
Participant milestones
| Measure |
Hh Pathway Activated
Pediatric patients with recurrent or refractory medulloblastoma with evidence of activation of Hedgehog (Hh) signaling pathway in their tumors.
|
|---|---|
|
Overall Study
STARTED
|
12
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
12
|
Reasons for withdrawal
| Measure |
Hh Pathway Activated
Pediatric patients with recurrent or refractory medulloblastoma with evidence of activation of Hedgehog (Hh) signaling pathway in their tumors.
|
|---|---|
|
Overall Study
Progression/Relapse
|
11
|
|
Overall Study
Adverse Event
|
1
|
Baseline Characteristics
Vismodegib in Treating Younger Patients With Recurrent or Refractory Medulloblastoma
Baseline characteristics by cohort
| Measure |
Hh Pathway Activated
n=12 Participants
Pediatric patients with recurrent or refractory medulloblastoma with evidence of activation of Hedgehog (Hh) signaling pathway in their tumors.
|
|---|---|
|
Age, Continuous
|
10.4 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 12 monthsObjective 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.
Outcome measures
| Measure |
Hh Pathway Activated
n=12 Participants
Pediatric patients with recurrent or refractory medulloblastoma with evidence of activation of Hedgehog (Hh) signaling pathway in their tumors.
|
|---|---|
|
Objective Response (CR+PR) Sustained for ≥ 8 Weeks
|
1 participants
|
PRIMARY outcome
Timeframe: up to 12 monthPopulation: Patients who have day 21 plasma GDC-0449 concentration data available
plasma GDC-0449 concentration of day 21 in first course
Outcome measures
| Measure |
Hh Pathway Activated
n=11 Participants
Pediatric patients with recurrent or refractory medulloblastoma with evidence of activation of Hedgehog (Hh) signaling pathway in their tumors.
|
|---|---|
|
Pharmacokinetics (Plasma) of GDC-0449
|
18 uM
Interval 9.5 to 45.3
|
SECONDARY outcome
Timeframe: From start of treatment up to 2 yearsProgression-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.
Outcome measures
| Measure |
Hh Pathway Activated
n=12 Participants
Pediatric patients with recurrent or refractory medulloblastoma with evidence of activation of Hedgehog (Hh) signaling pathway in their tumors.
|
|---|---|
|
Progression-free Survival
|
1.41 months
Interval 0.69 to 3.68
|
SECONDARY outcome
Timeframe: From start of treatment up to 2 yearsPopulation: Patient with sustained objective response
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.
Outcome measures
| Measure |
Hh Pathway Activated
n=1 Participants
Pediatric patients with recurrent or refractory medulloblastoma with evidence of activation of Hedgehog (Hh) signaling pathway in their tumors.
|
|---|---|
|
Duration of Objective Response
|
2.83 months
|
SECONDARY outcome
Timeframe: up to 12 monthPopulation: The calculation of drug penetration is based on patients who had the course 1 plasma and CSF drug concentration data
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.
Outcome measures
| Measure |
Hh Pathway Activated
n=11 Participants
Pediatric patients with recurrent or refractory medulloblastoma with evidence of activation of Hedgehog (Hh) signaling pathway in their tumors.
|
|---|---|
|
Pharmacokinetic Parameters of Vismodegib, CSF Penetration
|
0.14 penetration rate
Interval 0.07 to 0.28
|
Adverse Events
Hh Pathway Activated
Serious events: 4 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Hh Pathway Activated
n=12 participants at risk
Pediatric patients with recurrent or refractory medulloblastoma with evidence of activation of Hedgehog (Hh) signaling pathway in their tumors.
|
|---|---|
|
Investigations
Lymphocyte count decreased
|
25.0%
3/12 • Number of events 3
|
|
Gastrointestinal disorders
Nausea
|
8.3%
1/12 • Number of events 1
|
|
Investigations
Platelet count decreased
|
8.3%
1/12 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.3%
1/12 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
8.3%
1/12 • Number of events 1
|
Other adverse events
| Measure |
Hh Pathway Activated
n=12 participants at risk
Pediatric patients with recurrent or refractory medulloblastoma with evidence of activation of Hedgehog (Hh) signaling pathway in their tumors.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
25.0%
3/12 • Number of events 4
|
|
Eye disorders
Blurred vision
|
8.3%
1/12 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
8.3%
1/12 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
16.7%
2/12 • Number of events 3
|
|
Gastrointestinal disorders
Diarrhea
|
25.0%
3/12 • Number of events 3
|
|
Gastrointestinal disorders
Lip pain
|
8.3%
1/12 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
33.3%
4/12 • Number of events 4
|
|
Gastrointestinal disorders
Stomach pain
|
8.3%
1/12 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
50.0%
6/12 • Number of events 6
|
|
General disorders
Death NOS
|
16.7%
2/12 • Number of events 2
|
|
General disorders
Fatigue
|
50.0%
6/12 • Number of events 6
|
|
General disorders
Gait disturbance
|
8.3%
1/12 • Number of events 1
|
|
General disorders
Pain
|
8.3%
1/12 • Number of events 1
|
|
Investigations
Alanine aminotransferase increased
|
50.0%
6/12 • Number of events 8
|
|
Investigations
Aspartate aminotransferase increased
|
25.0%
3/12 • Number of events 3
|
|
Investigations
Lymphocyte count decreased
|
16.7%
2/12 • Number of events 4
|
|
Investigations
Neutrophil count decreased
|
8.3%
1/12 • Number of events 1
|
|
Investigations
Platelet count decreased
|
8.3%
1/12 • Number of events 1
|
|
Investigations
Weight loss
|
8.3%
1/12 • Number of events 1
|
|
Investigations
White blood cell decreased
|
16.7%
2/12 • Number of events 2
|
|
Metabolism and nutrition disorders
Anorexia
|
16.7%
2/12 • Number of events 2
|
|
Metabolism and nutrition disorders
Dehydration
|
8.3%
1/12 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
16.7%
2/12 • Number of events 3
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
16.7%
2/12 • Number of events 3
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
8.3%
1/12 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
8.3%
1/12 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypokalemia
|
16.7%
2/12 • Number of events 4
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
33.3%
4/12 • Number of events 4
|
|
Metabolism and nutrition disorders
Hyponatremia
|
8.3%
1/12 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
16.7%
2/12 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other (Specify, __)[mild cramping in hands.]
|
8.3%
1/12 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other (Specify, __)[muscle cramps in calf]
|
8.3%
1/12 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other (Specify, __)[Muscle Cramps.]
|
8.3%
1/12 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
25.0%
3/12 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
16.7%
2/12 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
8.3%
1/12 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
8.3%
1/12 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other specify[Generalized muscle aches]
|
8.3%
1/12 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other, specify[Leg muscle cramps]
|
8.3%
1/12 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other, specify[Muscle spasm/twitching]
|
8.3%
1/12 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other, specify[MUSCLE SPASMS/TWITCHING]
|
8.3%
1/12 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other, specify[muscle twitching]
|
8.3%
1/12 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
8.3%
1/12 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
8.3%
1/12 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
25.0%
3/12 • Number of events 3
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify
|
16.7%
2/12 • Number of events 2
|
|
Nervous system disorders
Depressed level of consciousness
|
8.3%
1/12 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
8.3%
1/12 • Number of events 1
|
|
Nervous system disorders
Dysarthria
|
16.7%
2/12 • Number of events 2
|
|
Nervous system disorders
Dysgeusia
|
16.7%
2/12 • Number of events 2
|
|
Nervous system disorders
Headache
|
33.3%
4/12 • Number of events 4
|
|
Nervous system disorders
Hydrocephalus
|
8.3%
1/12 • Number of events 1
|
|
Nervous system disorders
Movements involuntary
|
8.3%
1/12 • Number of events 1
|
|
Nervous system disorders
Paresthesia
|
8.3%
1/12 • Number of events 2
|
|
Psychiatric disorders
Anxiety
|
8.3%
1/12 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
8.3%
1/12 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
33.3%
4/12 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
8.3%
1/12 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
16.7%
2/12 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, specify
|
8.3%
1/12 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
8.3%
1/12 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
8.3%
1/12 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
8.3%
1/12 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Purpura
|
8.3%
1/12 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
8.3%
1/12 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Skin hypopigmentation
|
8.3%
1/12 • Number of events 1
|
|
Vascular disorders
Hot flashes
|
8.3%
1/12 • Number of events 1
|
Additional Information
Tong Lin (Biostatistician)
St. Jude Children's Research Hospital
Phone: 9015952048
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60