|Phase II, Phase I||Biomarker/Laboratory analysis, Treatment||Active||3 to 21||NCI||NCI-2011-02600|
CDR0000683459, COG-ACNS0927, ACNS0927, U10CA098543, U10CA97452, NCT01189266
This phase I/II trial is studying the side effects and best dose of vorinostat and to see how well it works when given together with radiation therapy followed by maintenance therapy with vorinostat in treating younger patients with newly diagnosed pontine gliomas. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving vorinostat together with radiation therapy may kill more tumor cells.
Further Study Information
l. To estimate the maximum-tolerated dose (MTD) or recommend a phase II dose of vorinostat given concurrently with radiotherapy in pediatric patients with newly diagnosed intrinsic pontine gliomas.
II. To define and describe the toxicities of vorinostat given concurrently with radiotherapy in these patients.
III. To determine, in the context of a this phase I/II trial, the antitumor activity of combining vorinostat with radiotherapy followed by maintenance vorinostat for 12 courses in these patients, as measured by 12-month event-free survival and overall survival.
IV. To determine the toxicities of vorinostat for 12 additional courses after completion of concurrent vorinostat and radiotherapy.
I. To measure non-homologous end-joining (NHEJ) activity in peripheral blood mononuclear cells (PBMCs) before treatment, at 2 weeks after starting vorinostat and radiotherapy, and at the end of radiotherapy.
II. To measure HDAC2 levels and assess histone acetylation in PBMCs before treatment, at 2 weeks after starting vorinostat and radiotherapy, and at the end of radiotherapy.
III. To quantify DNA repair proteins from the NHEJ and homologous recombination repair pathways in tumors by either Western analysis or IHC, if paraffin-embedded tumor is available.
OUTLINE: This is a multicenter, phase I, dose-escalation study of vorinostat followed by a phase II study.
Patients receive vorinostat orally or IV on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients undergo 3D-conformal or intensity-modulated radiotherapy 5 days per week for 6 weeks. Patients then receive maintenance therapy comprising oral vorinostat on days 1-28. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
Blood and tumor samples may be collected periodically for correlative studies.
After completion of study treatment, patients are followed up for up to 5 years.
- Newly diagnosed diffuse intrinsic pontine gliomas (defined as tumors with a pontine epicenter and diffuse involvement of ≥ 2/3 of the pons)
- Patients with brainstem tumors that do not meet these criteria or are not considered to be typical intrinsic pontine gliomas are eligible provided their tumors are biopsied and proven to be an anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, or anaplastic mixed glioma
- No patients with juvenile pilocytic astrocytoma, fibrillary astrocytoma, gangliogliomas, or other mixed gliomas without anaplasia
- No patients with disseminated disease (MRI of the spine must be performed if disseminated disease is suspected by the treating physician)
- Karnofsky performance status (PS) 50-100% (for patients > 16 years of age) or Lansky PS 50-100% (for patients ≤ 16 years of age)
- Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance status
- ANC ≥ 1,000/uL
- Platelet count ≥ 100,000/uL (transfusion independent, defined as not receiving platelet transfusions within the past 7 days)
- Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed)
- Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR a serum creatinine based on age/gender as follows:
- ≤ 0.8 mg/dL (for patients 3 to < 6 years of age)
- ≤ 1 mg/dL (for patients 6 to < 10 years of age)
- ≤ 1.2 mg/dL (for patients 10 to < 13 years of age)
- ≤ 1.4 mg/dL (for female patients ≥ 13 years of age)
- ≤ 1.5 mg/dL (for male patients 13 to < 16 years of age)
- ≤ 1.7 mg/dL (for male patients ≥ 16 years of age)
- Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 times upper limit of normal (ULN) for age
- ALT ≤ 110 U/L (for the purpose of this study, the ULN for ALT is 45 U/L)
- Serum albumin ≥ 2 g/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Able to swallow capsules or liquids
- Not dependent on NG tube feeding
- Patients with seizure disorder are eligible provided that they are not on enzyme-inducing anticonvulsants and seizures are well controlled
- No uncontrolled infection
- No patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
- No prior treatment except for dexamethasone and/or surgery
- At least 2 weeks since prior valproic acid
- More than 7 days since prior growth factors that support platelet or white cell number or function
- No other concurrent investigational drugs
- No other concurrent anticancer agents (including chemotherapy, immunotherapy, or biologic therapy)
- No concurrent coumadin, heparin, low-molecular weight heparin, or any other anticoagulants
- No concurrent aspirin (> 81 mg/day), NSAIDs, clopidogrel (Plavix), dipyridamole (Persantine), or any other drug that inhibits platelet function
- No concurrent enzyme-inducing anticonvulsants
Trial Lead Organizations/Sponsors
National Cancer Institute
|Jack Su||Principal Investigator|
|Jack Su||Ph: 832-822-4306|
|UAB Comprehensive Cancer Center|
|Alyssa T Reddy||Ph: 205-934-0309|
|Genesys Hurley Cancer Institute|
|Philip J. Stella||Ph: 734-712-3456|
|AnMed Cancer Center|
|James Dewitt Bearden||Ph: 800-486-5941|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01189266
ClinicalTrials.gov processed this data on October 17, 2013
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