GliomaPhase 2NCT03632317
A Study of Panobinostat in Combination With Everolimus for Children and Young Adults With Gliomas
A Phase 2 study testing Panobinostat and Everolimus in people with Glioma and Diffuse Intrinsic Pontine Glioma, run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial summary
This phase 2 trial will evaluate the activity of Panobinostat in combination with Everolimus for children with gliomas harboring H3.1 or H3.3K27M mutation, including newly diagnosed high-grade glioma or DIPG (diffuse intrinsic pontine glioma) after radiation (stratum A) and recurrent/progressive glioma (grade II-IV… Read more about this study
- Who is it for?
- Ages 2 to 30 years
- Conditions the study is for
- Glioma, Diffuse Intrinsic Pontine Glioma
- What is being tested?
- Panobinostat and Everolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2019to Oct 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 2 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- All patients and/or a legal guardian must sign institutionally approved written informed consent and assent documents.
- Patient must be greater than 2 years and less than 30 years
- BSA (body surface area) greater than 0.3 m2
- Functional status: Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for patients < 16 years of age (Karnofsky and Lansky is a scoring system used to quantify the general well being of cancer patients where 100% represents perfect health and 0% represents death). Neurologic deficits in patients with CNS tumors must have been relatively stable for a minimum of 7 days. Patients who are unable to walk because of paralysis, but who are able to sit in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
- Adequate bone marrow function
- Adequate liver function
Show all 21Show fewer
- Adequate renal and metabolic function
- Urine protein:creatinine (UPC) ratio of < 1; or a urinalysis that is negative for protein; or 24-hour urine protein level < 1000 mg/dL
- Patients must have Magnesium > 1.5 mg/dL and potassium > 3.5 mmol/L
- Patients with known seizure disorder must have seizures adequately controlled with non- enzyme inducing antiepileptic medications
- No increase in steroid dose within the past 7 days.
- STRATUM A: histological confirmation of a newly diagnosed high-grade glioma or DIPG or STRATUM B: histological confirmation of a recurrent or progressive grade II-IV glioma (including DIPG) [histology can come from tissue at diagnosis or relapse]
- Primary brain or spine tumor are eligible, including tumors with metastases, multiple lesions
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy.
- Myelosuppressive chemotherapy: Must not have received within 3 weeks (6 weeks if prior nitrosourea).
- Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor, 14 days for long-acting (e.g. PEG-filgrastim)
- Biologic (anti-neoplastic agent): At least 7 days or 3 half-lives (whichever is longer) since the completion of therapy with a biologic agent.
- Radiation therapy: Strata A: ≥ 2 weeks and ≤ to 12 weeks must have elapsed from radiation. Strata B: ≥ 2 weeks must have elapsed from focal radiation.
- Surgery: > 3 weeks from major surgery. If recent craniotomy, adequate wound healing must be determined by neurosurgical team.
- Autologous Stem Cell Transplant or Rescue: No evidence of active graft vs. host disease and ≥ 4 weeks must have elapsed.
- H3K27M mutation: Participants must have a mutation in H3.3 K27M or H3.1 K27M as identified by tumor (FFPE or fresh, diagnosis or relapse tissue, but relapse tissue preferred) sequencing, or by CLIA-certified immunohistochemistry staining positive for H3K27M, as defined by review by U of M neuro-pathology.
Who cannot join
- Patients who are breastfeeding, pregnant or refuse to use an effective form of birth control are excluded. Abstinence is considered an effective form of birth control.
- Patients with uncontrolled infection are excluded.
- Inability to swallow oral pill (panobinostat does not have liquid formulation).
- Other medications: Patients receiving other anti-neoplastic agents are excluded; patients on enzyme-inducing anticonvulsive agents are excluded; patients requiring strong CYP3A4 or PGP inducers or inhibitors are excluded; patients on steroids for symptom management must be on a stable dose for 7 days prior to start of treatment.
- Allogeneic stem cell transplant: Patients within 1 year of allogeneic stem cell transplant, patients with active GVHD or requiring immunosuppression are excluded.
- Previous hypersensitivity to rapamycin or rapamycin derivatives.
- Baseline QTc of >450 msec on EKG OR electrolyte imbalance predisposing to QTc prolongation (baseline ≥ Grade 1 hypokalemia or hyperkalemia; and baseline ≥ Grade 2 Ca++, Mg++, phosphate abnormalities). Repletion/correction is allowed to achieve eligibility. Use of QTC prolonging medications will be monitored throughout the trial.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Michigan Cancer Center
Ann Arbor, Michigan, 48109
About this study
Official title: A Phase 2 Study of Panobinostat in Combination With Everolimus for Children and Young Adults With Gliomas Harboring H3.3 or H3.1 K27M Mutation
This phase 2 trial will evaluate the activity of Panobinostat in combination with Everolimus for children with gliomas harboring H3.1 or H3.3K27M mutation, including newly diagnosed high-grade glioma or DIPG (diffuse intrinsic pontine glioma) after radiation (stratum A) and recurrent/progressive glioma (grade II-IV, including DIPG) (stratum B).
- Conditions
- Glioma, Diffuse Intrinsic Pontine Glioma
- Being tested
- Panobinostat, Everolimus
- Keywords
- H3.1K27M, H3.3K27M, diffuse intrinsic pontine glioma, DIPG, high-grade glioma, pediatric glioma, H3K27M, panobinostat
- Medical subject headings
- Glioma, Diffuse Intrinsic Pontine Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PanobinostatDrug
30 mg/m^2
EverolimusDrug
3.0 mg/m^2
| Study group | Role | What they receive |
|---|---|---|
| Panobinostat and Everolimus | Experimental | Panobinostat daily M, W, F for 2 weeks every 28 days for the first cycle (28 days). After first cycle Panobinostat daily M, W, F for 2 weeks every 28 days combined with Everolimus daily. Receives: Drug: Panobinostat; Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median Progression Free Survival (PFS) at 1 Year
Median PFS at 1 year for stratum A will be measured. Progression is defined as > 25% increase in the size of the tumor or appearance of new lesions.
Measured: 1year
Median Progression Free Survival (PFS) at 2 Years
Median PFS at 1 year for stratum A will be measured. Progression is defined as > 25% increase in the size of the tumor or appearance of new lesions.
Measured: 2years
Overall Survival at 1Year
The proportion of patients alive at 1 year for stratum A.
Measured: 1year
Overall Survival at 2Years
The proportion of patients alive at 2 years for stratum A.
Measured: 2years
Overall Response Rate (ORR) After Two Cycles of Panobinostat + Everolimus
Overall Response Rate (ORR) After Two Cycles of Panobinostat + Everolimus for stratum B. Overall response is defined as a partial or complete response. Partial response is defined as a ≥50% decrease in size of tumor in comparison to baseline measurements. Complete response is defined as the disappearance of all abnormal signal. This includes return to normal size of the brainstem for brainstem lesions.
Measured: 84 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2018
- Study startOct 2019 (estimated)
- Primary completionOct 2025 (estimated)
- Study completionOct 2025 (estimated)
Why it stopped: low accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GliomaStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe 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
- Model description
- Patients will be divided into two stratums; newly diagnosed high-grade glioma or DIPG after radiation (stratum A) and recurrent/progressive glioma (grade II-IV, including DIPG) (stratum B).
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Carl Koschmann, MD, Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03632317
- Sponsor's protocol ID
- UMCC 2018.006
- Other IDs
- HUM00140679
- Status last verified
- Aug 2019
- First submitted
- 13 Aug 2018
- Last updated
- 19 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Panobinostat in Combination With Everolimus for Children and Young Adults With Gliomas Harboring H3.3 or H3.1 K27M Mutation
- ClinicalTrials.gov ID
- NCT03632317
- Acronym / sponsor ID
- UMCC 2018.006
- Conditions
- Glioma, Diffuse Intrinsic Pontine Glioma
- Keywords
- H3.1K27M, H3.3K27M, diffuse intrinsic pontine glioma, DIPG, high-grade glioma, pediatric glioma, H3K27M, panobinostat
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: low accrual
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- Oct 2019 (estimated)
- Primary completion
- Oct 2025 (estimated)
- Study completion
- Oct 2025 (estimated)
- First posted
- 15 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase 2 trial will evaluate the activity of Panobinostat in combination with Everolimus for children with gliomas harboring H3.1 or H3.3K27M mutation, including newly diagnosed high-grade glioma or DIPG (diffuse intrinsic pontine glioma) after radiation (stratum A) and recurrent/progressive glioma (grade II-IV, including DIPG) (stratum B).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patients will be divided into two stratums; newly diagnosed high-grade glioma or DIPG after radiation (stratum A) and recurrent/progressive glioma (grade II-IV, including DIPG) (stratum B).
| Arm | Type | Receives |
|---|---|---|
| Panobinostat and Everolimus | Experimental | Drug: Panobinostat, Drug: EverolimusPanobinostat daily M, W, F for 2 weeks every 28 days for the first cycle (28 days). After first cycle Panobinostat daily M, W, F for 2 weeks every 28 days combined with Everolimus daily. |
Who may qualify
- Ages
- 2 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (21 listed)
- All patients and/or a legal guardian must sign institutionally approved written informed consent and assent documents.
- Patient must be greater than 2 years and less than 30 years
- BSA (body surface area) greater than 0.3 m2
- Functional status: Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for patients < 16 years of age (Karnofsky and Lansky is a scoring system used to quantify the general well being of cancer patients where 100% represents perfect health and 0% represents death). Neurologic deficits in patients with CNS tumors must have been relatively stable for a minimum of 7 days. Patients who are unable to walk because of paralysis, but who are able to sit in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
- Adequate bone marrow function
Key exclusion criteria (7 listed)
- Patients who are breastfeeding, pregnant or refuse to use an effective form of birth control are excluded. Abstinence is considered an effective form of birth control.
- Patients with uncontrolled infection are excluded.
- Inability to swallow oral pill (panobinostat does not have liquid formulation).
- Other medications: Patients receiving other anti-neoplastic agents are excluded; patients on enzyme-inducing anticonvulsive agents are excluded; patients requiring strong CYP3A4 or PGP inducers or inhibitors are excluded; patients on steroids for symptom management must be on a stable dose for 7 days prior to start of treatment.
- Allogeneic stem cell transplant: Patients within 1 year of allogeneic stem cell transplant, patients with active GVHD or requiring immunosuppression are excluded.
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 |
|---|---|---|
| Panobinostat30 mg/m^2 | Drug | Panobinostat and Everolimus |
| Everolimus3.0 mg/m^2 | Drug | Panobinostat and Everolimus |
Primary outcome
Median Progression Free Survival (PFS) at 1 Year
Time frame: 1year
Median PFS at 1 year for stratum A will be measured. Progression is defined as > 25% increase in the size of the tumor or appearance of new lesions.
Median Progression Free Survival (PFS) at 2 Years
Time frame: 2years
Median PFS at 1 year for stratum A will be measured. Progression is defined as > 25% increase in the size of the tumor or appearance of new lesions.
Overall Survival at 1Year
Time frame: 1year
The proportion of patients alive at 1 year for stratum A.
Overall Survival at 2Years
Time frame: 2years
The proportion of patients alive at 2 years for stratum A.
Overall Response Rate (ORR) After Two Cycles of Panobinostat + Everolimus
Time frame: 84 Days
Overall Response Rate (ORR) After Two Cycles of Panobinostat + Everolimus for stratum B. Overall response is defined as a partial or complete response. Partial response is defined as a ≥50% decrease in size of tumor in comparison to baseline measurements. Complete response is defined as the disappearance of all abnormal signal. This includes return to normal size of the brainstem for brainstem lesions.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2019.
- Individual participant dataSharing planned: No
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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.
Carl Koschmann, MD principal investigator
University of Michigan Rogel Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Panobinostat and Everolimus in people with Glioma and Diffuse Intrinsic Pontine Glioma, run by University of Michigan Rogel Cancer Center at 1 site 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 7 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: withdrawn, as of the sponsor's last update on 19 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Median Progression Free Survival (PFS) at 1 Year (time frame: 1year). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Aug 2019.