Clinical Trials Logo

Clinical Trial Details — Status: Withdrawn

Administrative data

NCT number NCT03632317
Other study ID # UMCC 2018.006
Secondary ID HUM00140679
Status Withdrawn
Phase Phase 2
First received
Last updated
Start date October 2019
Est. completion date October 2025

Study information

Verified date August 2019
Source University of Michigan Rogel Cancer Center
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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, including DIPG) (stratum B).


Recruitment information / eligibility

Status Withdrawn
Enrollment 0
Est. completion date October 2025
Est. primary completion date October 2025
Accepts healthy volunteers No
Gender All
Age group 2 Years to 30 Years
Eligibility Inclusion Criteria:

- 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

- 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.

Exclusion Criteria:

- 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Panobinostat
30 mg/m^2
Everolimus
3.0 mg/m^2

Locations

Country Name City State
United States University of Michigan Cancer Center Ann Arbor Michigan

Sponsors (1)

Lead Sponsor Collaborator
University of Michigan Rogel Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. 1year
Primary 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. 2years
Primary Overall Survival at 1Year The proportion of patients alive at 1 year for stratum A. 1year
Primary Overall Survival at 2Years The proportion of patients alive at 2 years for stratum A. 2years
Primary 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. 84 Days
See also
  Status Clinical Trial Phase
Active, not recruiting NCT04539574 - An Investigational Scan (7T MRI) for the Imaging of Central Nervous System Tumors N/A
Enrolling by invitation NCT04461002 - Evaluation of the Correlation Between Molecular Phenotype and Radiological Signature (by PET-scanner and MRI) of Incident WHO II and III Grade Gliomas.
Terminated NCT01902771 - Dendritic Cell Vaccine Therapy With In Situ Maturation in Pediatric Brain Tumors Phase 1
Completed NCT03242824 - The Utility of 18F-DOPA-PET in the Treatment of Recurrent High-grade Glioma Phase 2
Recruiting NCT04186832 - Step Count Monitoring as a Measure of Physical Activity in Patients With Newly Diagnosed Glioma Undergoing Radiation Therapy N/A
Completed NCT00424554 - Low-dose Temozolomide for 2 Weeks on Brain Tumor Enzyme in Patients With Gliomas (P04602 AM1) (Completed) Phase 2
Recruiting NCT05968053 - Detection of Microplastics and Nanoplastics in Neurosurgery Patients (DT-MiNi)
Not yet recruiting NCT04550663 - NKG2D CAR-T(KD-025) in the Treatment of Relapsed or Refractory NKG2DL+ Tumors Phase 1
Completed NCT02805179 - A Study of High-Dose Chemoradiation Using Biologically-Based Target Volume Definition in Patients With Glioblastoma Phase 2
Terminated NCT04556929 - Enhanced Detection in Glioma Excision N/A
Not yet recruiting NCT06408428 - Glioma Intraoperative MicroElectroCorticoGraphy N/A
Recruiting NCT06043232 - MMR/MSI Phenotypes in Prediction of Tumor Vaccine Benefit for Gliomas
Not yet recruiting NCT06043765 - Reducing Cognitive Impairment in Glioma With Repetitive Transcranial Magnetic Stimulation and Cognitive Strategy Training N/A
Not yet recruiting NCT05025969 - Evaluation of the Incidence of NTRK Gene Fusion in Adult Brain Tumours
Completed NCT02978261 - Study of a c-Met Inhibitor PLB1001 in Patients With PTPRZ1-MET Fusion Gene Positive Recurrent High-grade Gliomas Phase 1
Terminated NCT01502605 - Phase I Study of Orally Administered Aminolevulinic Acid for Resection of Malignant Astrocytomas Phase 1
Completed NCT01836536 - Search for a Link Between Response to Treatment and Circulating Leucocytes in High Grade Glioma Patients N/A
Completed NCT01479686 - iMRI Guided Resection in Cerebral Glioma Surgery Phase 3
Completed NCT01212731 - Skull Base and Low Grade Glioma Neurocognitive Magnetic Resonance Imaging (MRI) Study
Withdrawn NCT00985036 - Vascular Endothelial Growth Factor (VEGF) Levels in Brain Tumor Patients N/A