Adult MedulloblastomaPhase 2NCT00939484
Vismodegib in Treating Patients With Recurrent or Refractory Medulloblastoma
A Phase 2 study testing Pharmacological Study and Vismodegib in people with Adult Medulloblastoma, run by National Cancer Institute (NCI) at 13 sites in United States.
Trial summary
This phase II trial is studying how well vismodegib works in treating adult patients with recurrent or refractory medulloblastoma. Vismodegib may slow the growth of tumor cells and may be an effective treatment for medulloblastoma. Read more about this study
- Who is it for?
- Ages 22 years and older
- Conditions the study is for
- Adult Medulloblastoma
- What is being tested?
- Pharmacological Study and Vismodegib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 13 sitesUnited States
- Study dates
- Jun 2009to Aug 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with a histologically confirmed diagnosis of medulloblastoma (including posterior fossa PNET) that is recurrent, progressive, or refractory to standard therapy and for which there is no known curative therapy are eligible; there must be evidence of residual measurable disease or lesion in pre-study MRI as described in section; patients with spinal disease that is measurable will be eligible
- The diagnosis should be confirmed at the treating institution and tissue (either from the diagnosis or relapse or preferably from both time points) must be available for biological studies
- Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration; this is to be documented in the database
- Eastern Cooperative Oncology Group (ECOG) performance status 0- 2
- No other myelosuppressive chemotherapy or immunotherapy within 4 weeks prior to study entry (6 weeks if prior nitrosourea)
- Decadron dose should also be stable or decreasing for at least 1 week (7days) prior to starting therapy
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- Radiation therapy (XRT) >= 3 months prior to study entry for craniospinal irradiation (>= 23 Gy); >= 8 weeks for local irradiation to primary tumor; >= 2 weeks prior to study entry for focal irradiation for symptomatic metastatic sites
- Off all colony stimulating factors >= 1 week prior to study entry (GCSF, GM CSF, erythropoietin)
- Absolute neutrophil count (ANC) >= 1000/μL
- Platelet count >= 50,000/uL (transfusion independent)
- Hemoglobin >= 8.0 gm/dL (may receive RBC transfusions)
- Creatinine clearance or radio-isotope GFR >= 70ml/min/1.73 m2 or
- A serum creatinine =< 2.0 mg/dL
- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
- Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x institutional ULN
- Serum glutamic-oxalacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2.5 times institutional ULN
- Serum albumin >= 2.5 g/dL
- Patient must have recovered from the significant acute toxicities of all prior therapy before entering this study and meet all other eligibility criteria
- Pregnancy should be avoided for 12 months after the last dose of GDC-0449 for females of child-bearing potential; female patients of childbearing potential must not be pregnant or breast-feeding; female patients of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to beginning treatment
- Women of childbearing potential are required to use 2 forms of acceptable contraception, including one barrier method during participation in the study and for the 12 months following the last dose; for medical or personal reasons, 100% commitment to abstinence is considered an acceptable form of birth control. All patients should receive contraceptive counseling either by the investigator, or by an OB/gynecologist or other physician who is qualified in this area of expertise; prior to dispensing GDC-0449, the investigator must confirm and document the patient's use of two contraceptive methods, dates of negative pregnancy test, and confirm the patient's understanding of the of GDC-0449 to cause spontaneous abortion or birth defects
- Signed informed consent according to institutional guidelines must be obtained
Who cannot join
- Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patient's ability to tolerate protocol therapy or would likely interfere with the study procedures or results
- Patients receiving any other anticancer or investigational drug therapy
- Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
- Life expectancy < 12 weeks as determined by treating physician
- Inability to swallow capsules
- Prior treatment with GDC-0449 or other antagonists of the HH pathway
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- Malabsorption syndrome or other condition that would interfere with enteral absorption
- History of congestive heart failure
- History of ventricular arrhythmia requiring medication
- Uncontrolled hypocalcemia, hypomagnesemia, hyponatremia or hypokalemia defined as less than the lower limit of normal for the institution despite adequate electrolyte supplementation
- Congenital long QT syndrome
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Duke University Medical Center
Durham, North Carolina, 27710
Baylor College of Medicine
Houston, Texas, 77030
Children's Hospital Los Angeles
Los Angeles, California, 90027
Pediatric Brain Tumor Consortium
Memphis, Tennessee, 38105
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
UCSF Medical Center-Mount Zion
San Francisco, California, 94115
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: A Phase II Clinical Trial Evaluating the Efficacy and Safety of GDC-0449 in Adults With Recurrent or Refractory Medulloblastoma
This phase II trial is studying how well vismodegib works in treating adult patients with recurrent or refractory medulloblastoma. Vismodegib may slow the growth of tumor cells and may be an effective treatment for medulloblastoma.
Read the detailed description
PRIMARY OBJECTIVES:
- To estimate the efficacy of GDC-0449 (vismodegib) treatment for adult patients with recurrent or refractory medulloblastoma, as measured by the objective response rates for patients without (Stratum A) and with (Stratum B) evidence of activation of Sonic Hedgehog (SHH) signaling pathway tumors.
SECONDARY OBJECTIVES:
- To assess the safety and tolerability of GDC-0449 administered on a once daily schedule.
II. To estimate the duration of objective response and progression-free survival (PFS).
III. To characterize the pharmacokinetics (plasma and cerebrospinal fluid) of GDC-0449 in adults with refractory medulloblastoma.
IV. To document pathologic and genomic methods to identify CNS tumors with activation of the PTCH/SHH pathway.
- To describe the objective responses observed in patients whose pathologic assessment of tumor result in unknown (Stratum C) evidence of activation of Sonic Hedgehog (SHH) signaling pathway tumors.
OUTLINE: This is a multicenter study. Patients are stratified according to PTCH/Sonic Hedgehog signaling pathway activation (inactivated vs activated vs unknown).
Patients receive vismodegib orally (PO) once daily on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically for up to 12 months.
- Conditions
- Adult Medulloblastoma
- Being tested
- Pharmacological Study, Vismodegib
- Medical subject headings
- Medulloblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Correlative studies
VismodegibDrug
Also called Erivedge, GDC-0449, Hedgehog Antagonist GDC-0449
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (vismodegib) | Experimental | Patients receive vismodegib PO once daily on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity. Receives: Other: Pharmacological Study; Drug: Vismodegib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response (CR+PR) Sustained for ≥ 8 Weeks
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.
Measured: Up to 12 months
Secondary outcomes (3)
Progression-free Survival
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.
Measured: From start of treatment up to 2 years
Duration of 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.
Measured: From start of treatment up to 2 years
Pharmacokinetic Parameters of Vismodegib, CSF Penetration
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.
Measured: up to 12 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2009 (estimated)
- Study startJun 2009
- Primary completionMay 2013
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adult MedulloblastomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Amar Gajjar, Principal investigator, Pediatric Brain Tumor Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00939484
- Sponsor's protocol ID
- NCI-2012-03020
- Other IDs
- NCI-2012-03020, PBTC-025B, PBTC-025B, U01CA081457
- Status last verified
- Mar 2015
- First submitted
- 14 Jul 2009
- Last updated
- 25 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Robinson GW, Orr BA, Wu G, Gururangan S, Lin T, Qaddoumi I, Packer RJ, Goldman S, Prados MD, Desjardins A, Chintagumpala M, Takebe N, Kaste SC, Rusch M, Allen SJ, Onar-Thomas A, Stewart CF, Fouladi M, Boyett JM, Gilbertson RJ, Curran T, Ellison DW, Gajjar A. Vismodegib Exerts Targeted Efficacy Against Recurrent Sonic Hedgehog-Subgroup Medulloblastoma: Results From Phase II Pediatric Brain Tumor Consortium Studies PBTC-025B and PBTC-032. J Clin Oncol. 2015 Aug 20;33(24):2646-54. doi: 10.1200/JCO.2014.60.1591. Epub 2015 Jul 13.
PubMed 26169613
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Clinical Trial Evaluating the Efficacy and Safety of GDC-0449 in Adults With Recurrent or Refractory Medulloblastoma
- ClinicalTrials.gov ID
- NCT00939484
- Acronym / sponsor ID
- NCI-2012-03020
- Conditions
- Adult Medulloblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jun 2009
- Primary completion
- May 2013 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 15 Jul 2009 (estimated)
- Results
- Posted 25 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial is studying how well vismodegib works in treating adult patients with recurrent or refractory medulloblastoma. Vismodegib may slow the growth of tumor cells and may be an effective treatment for medulloblastoma.
Detailed description
PRIMARY OBJECTIVES:
- To estimate the efficacy of GDC-0449 (vismodegib) treatment for adult patients with recurrent or refractory medulloblastoma, as measured by the objective response rates for patients without (Stratum A) and with (Stratum B) evidence of activation of Sonic Hedgehog (SHH) signaling pathway tumors.
SECONDARY OBJECTIVES:
- To assess the safety and tolerability of GDC-0449 administered on a once daily schedule.
II. To estimate the duration of objective response and progression-free survival (PFS).
III. To characterize the pharmacokinetics (plasma and cerebrospinal fluid) of GDC-0449 in adults with refractory medulloblastoma.
IV. To document pathologic and genomic methods to identify CNS tumors with activation of the PTCH/SHH pathway.
- To describe the objective responses observed in patients whose pathologic assessment of tumor result in unknown (Stratum C) evidence of activation of Sonic Hedgehog (SHH) signaling pathway tumors.
OUTLINE: This is a multicenter study. Patients are stratified according to PTCH/Sonic Hedgehog signaling pathway activation (inactivated vs activated vs unknown).
Patients receive vismodegib orally (PO) once daily on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically for up to 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (vismodegib) | Experimental | Other: Pharmacological Study, Drug: VismodegibPatients receive vismodegib PO once daily on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 22 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Patients with a histologically confirmed diagnosis of medulloblastoma (including posterior fossa PNET) that is recurrent, progressive, or refractory to standard therapy and for which there is no known curative therapy are eligible; there must be evidence of residual measurable disease or lesion in pre-study MRI as described in section; patients with spinal disease that is measurable will be eligible
- The diagnosis should be confirmed at the treating institution and tissue (either from the diagnosis or relapse or preferably from both time points) must be available for biological studies
- Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration; this is to be documented in the database
- Eastern Cooperative Oncology Group (ECOG) performance status 0- 2
- No other myelosuppressive chemotherapy or immunotherapy within 4 weeks prior to study entry (6 weeks if prior nitrosourea)
Key exclusion criteria (11 listed)
- Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patient's ability to tolerate protocol therapy or would likely interfere with the study procedures or results
- Patients receiving any other anticancer or investigational drug therapy
- Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
- Life expectancy < 12 weeks as determined by treating physician
- Inability to swallow capsules
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pharmacological StudyCorrelative studies | Other | Treatment (vismodegib) |
| VismodegibAlso: Erivedge, GDC-0449, Hedgehog Antagonist GDC-0449Given PO | Drug | Treatment (vismodegib) |
Primary outcome
Objective Response (CR+PR) Sustained for ≥ 8 Weeks
Time frame: Up to 12 months
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.
3 secondary outcomes
Progression-free Survival
Time frame: From start of treatment up to 2 years
Duration of Objective Response
Time frame: From start of treatment up to 2 years
Pharmacokinetic Parameters of Vismodegib, CSF Penetration
Time frame: up to 12 month
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26169613Robinson GW, Orr BA, Wu G, Gururangan S, Lin T, Qaddoumi I, Packer RJ, Goldman S, Prados MD, Desjardins A, Chintagumpala M, Takebe N, Kaste SC, Rusch M, Allen SJ, Onar-Thomas A, Stewart CF, Fouladi M, Boyett JM, Gilbertson RJ, Curran T, Ellison DW, Gajjar A. Vismodegib Exerts Targeted Efficacy Against Recurrent Sonic Hedgehog-Subgroup Medulloblastoma: Results From Phase II Pediatric Brain Tumor Consortium Studies PBTC-025B and PBTC-032. J Clin Oncol. 2015 Aug 20;33(24):2646-54. doi: 10.1200/JCO.2014.60.1591. Epub 2015 Jul 13.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amar Gajjar principal investigator
Pediatric Brain Tumor Consortium
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pharmacological Study and Vismodegib in people with Adult Medulloblastoma, run by National Cancer Institute (NCI) at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response (CR+PR) Sustained for ≥ 8 Weeks (time frame: Up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00939484, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2016.