A Study of Panobinostat in Combination With Everolimus for Children and Young Adults With Gliomas

U

University of Michigan Rogel Cancer Center

Status and phase

Withdrawn
Phase 2

Conditions

Glioma
Diffuse Intrinsic Pontine Glioma

Treatments

Drug: Panobinostat
Drug: Everolimus

Study type

Interventional

Funder types

Other

Identifiers

NCT03632317
HUM00140679 (Other Identifier)
UMCC 2018.006

Details and patient eligibility

About

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).

Sex

All

Ages

2 to 30 years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

0 participants in 1 patient group

Panobinostat and Everolimus
Experimental group
Description:
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.
Treatment:
Drug: Everolimus
Drug: Panobinostat

Trial contacts and locations

1

Loading...

Data sourced from clinicaltrials.gov

Clinical trials

Find clinical trialsTrials by location
© Copyright 2024 Veeva Systems