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PTC299 in Treating Young Patients With Refractory or Recurrent Primary Central Nervous System Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01158300
Recruitment Status : Completed
First Posted : July 8, 2010
Last Update Posted : May 4, 2015
National Cancer Institute (NCI)
PTC Therapeutics
Information provided by (Responsible Party):
Pediatric Brain Tumor Consortium

Brief Summary:

RATIONALE: PTC299 may stop the growth of tumor cells by blocking blood flow to the tumor.

PURPOSE: This phase I trial is studying the side effects and the best dose of PTC299 in treating young patients with recurrent or refractory primary central nervous system tumors.

Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Drug: VEGF inhibitor PTC299 Phase 1

Detailed Description:



  • To estimate the maximum-tolerated dose and the recommended phase II dose of VEGF inhibitor PTC299 (PTC299) in pediatric patients with recurrent or progressive primary central nervous system (CNS) tumors.
  • To evaluate and characterize the adverse events associated with this regimen in these patients.
  • To evaluate and characterize the pharmacokinetics and pharmacodynamics of this regimen in these patients.


  • To investigate the relationships between PTC299 plasma exposure and other outcomes measures.
  • To evaluate the antitumor activity of this regimen in these patients.
  • To evaluate changes in angiogenic and inflammatory markers in the blood and the relationship between these changes and other outcome measures.
  • To obtain preliminary evidence of biologic activity of PTC299 by using magnetic resonance diffusion to assess tumor cellularity.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive oral VEGF inhibitor PTC299 twice or thrice daily. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and periodically during study for pharmacokinetic and pharmacodynamic studies by ELISA.

After completion of study therapy, patients are followed up for 30 days.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I and Pharmacokinetic Trial of PTC299 in Pediatric Patients With Refractory or Recurrent CNS Tumors
Study Start Date : November 2010
Actual Primary Completion Date : January 2015
Actual Study Completion Date : January 2015

Intervention Details:
  • Drug: VEGF inhibitor PTC299
    This is a dose escalation study. Study participants will receive .6 or 1.2 mg/kg orally twice daily or 1.2, 1.5, or 2.0 mg/kg orally three times daily for four consecutive weeks (a course). In the absence of unacceptable toxicity or disease progression, treatment may continue for up to 12 courses (approximately one year)

Primary Outcome Measures :
  1. Maximum-tolerated dose [ Time Frame: First four weeks of treatment ]
  2. Adverse events [ Time Frame: From the first day of treatment until 30 days after the last dose ]

Secondary Outcome Measures :
  1. Percentage of study participants with complete response or partial response to the study treatment [ Time Frame: Every 8 weeks ]
    Brain images to assess partial or complete response are performed every 8 weeks after the first dose of the study drug.

  2. Pharmacokinetics [ Time Frame: Day 1 and day 28 of course 1 ]
    Blood samples from study participants will be collected on day 1 and day 28 of course 1 for standard full pharmacokinetic studies.

  3. Change from baseline in blood angiogenic markers and cytokines at discontinuation or completion of treatment [ Time Frame: Before the first dose of drug on day 1 of course 1 and at the discontinuation or completion of treatment ]
    Blood samples will be collected and analyzed on Day 1 of pre-AM dosing at baseline and at the discontinuation or completion of treatment. Changes from baseline in blood angiogenic markers and cytokines (VEGF-A, VEGF-C, VEGF-D, PlGF, VEGFR-1, VEGFR-2, IL-6, and IL-8) will be assessed.

Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed diagnosis of primary central nervous system (CNS) malignancy at time of diagnosis or recurrence

    • Histology verification not required for intrinsic brain stem tumors and optic pathway gliomas

      • Must have radiographic evidence of progression
  • Recurrent, progressive, or refractory disease to standard therapy and for which there is no known curative therapy


  • Karnofsky performance status (PS) 50-100% (patients > 16 years of age) OR Lansky PS 50-100% (patients ≤ 16 years of age)
  • Body weight ≥ 15 kg and ≤ 100 kg
  • Patients with neurological deficits allowed provided they are stable for ≥ 1 week
  • Able to swallow capsules
  • ANC ≥ 1,000/μL (unsupported)
  • Platelet count ≥ 100,000/μL (unsupported)
  • Hemoglobin ≥ 8 g/dL (may be supported)
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 mL/min/1.73 m^2 OR serum creatinine normal based on age as follows:

    • 0.8 mg/dL (≤ 5 years of age)
    • 1.0 mg/dL (> 5 to ≤ 10 years of age)
    • 1.2 mg/dL (> 10 to ≤ 15 years of age)
    • 1.5 mg/dL (> 15 years of age)
  • Urine protein/creatinine ratio < 1.0
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT and AST ≤ 2.5 times ULN
  • Albumin ≥ 2.5 g/dL
  • PT and activated PTT ≤ 1.2 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No clinically significant unrelated systemic illness that would compromise the patient's ability to tolerate protocol therapy, or would likely interfere with the study procedures or results, including any of the following:

    • Serious infections including ongoing systemic bacterial, fungal, or viral infection
    • Significant cardiac, pulmonary, hepatic, or other organ dysfunction
  • Willing and able to comply with schedule visits, drug administration plan, laboratory tests, including pharmacokinetic and pharmacodynamic assessments, or other study procedures
  • No known coagulopathy or bleeding diathesis
  • No known history of drug-induced liver injury
  • No CNS, pulmonary, gastrointestinal, or urinary bleeding within the past month
  • No uncontrolled systemic hypertension (systolic BP or diastolic BP > 95% percentile for age)
  • No alcohol or drug addiction
  • Able to tolerate periodic MRI scans and gadolinium contrast


  • See Disease Characteristics
  • Recovered from the acute toxic of all prior therapy (excluding alopecia and neurotoxicity)
  • At least 3 weeks since prior myelosuppressive anticancer chemotherapy (6 weeks for nitrosourea)
  • At least 14 days since prior investigational or biological agent

    • At least 3 half-lives since prior biological agents that have a prolonged half-life
  • At least 3 half-lives since prior monoclonal antibody
  • At least 2 weeks since prior local palliative radiotherapy
  • At least 6 weeks since prior total-body irradiation, craniospinal radiotherapy, or radiotherapy to ≥ 50% of the pelvis
  • At least 90 days since prior allogeneic bone marrow transplantation

    • No active graft-versus-host disease
  • Concurrent dexamethasone or other corticosteroids allowed provided dose is stable for ≥ 7 days
  • At least 1 week since prior colony-forming growth factors (e.g., filgrastim, sargramostim, erythropoietin)

    • At least 14 days since long-acting colony-forming growth factor formulations (e.g., pegfilgrastim)
  • More than 4 weeks since prior major surgical procedures

    • More than 2 weeks since prior intermediate surgical procedures
    • More than 7 days since minor surgical procedures
  • No other concurrent anticancer or investigational drug therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01158300

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United States, California
UCSF Cancer Center and Cancer Research Institute
San Francisco, California, United States, 94143-0128
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-4318
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
Houston, Texas, United States, 77030-2399
Sponsors and Collaborators
Pediatric Brain Tumor Consortium
National Cancer Institute (NCI)
PTC Therapeutics
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Principal Investigator: Roger J. Packer, MD Children's Research Institute

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Responsible Party: Pediatric Brain Tumor Consortium Identifier: NCT01158300     History of Changes
Other Study ID Numbers: CDR0000680634
U01CA081457 ( U.S. NIH Grant/Contract )
PBTC-031 ( Other Identifier: Pediatric Brain Tumor Consortium )
PTC299-ONC-010-PBT ( Other Identifier: PTC Therapeutics )
First Posted: July 8, 2010    Key Record Dates
Last Update Posted: May 4, 2015
Last Verified: May 2015

Keywords provided by Pediatric Brain Tumor Consortium:
recurrent childhood malignant germ cell tumor
recurrent childhood brain stem glioma
recurrent childhood brain tumor
recurrent childhood central nervous system embryonal tumor
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
recurrent childhood ependymoma
recurrent childhood medulloblastoma
recurrent childhood pineoblastoma
recurrent childhood rhabdomyosarcoma
recurrent childhood spinal cord neoplasm
recurrent childhood subependymal giant cell astrocytoma
recurrent childhood visual pathway and hypothalamic glioma
recurrent childhood visual pathway glioma
childhood central nervous system choriocarcinoma
childhood central nervous system germ cell tumor
childhood central nervous system germinoma
childhood central nervous system mixed germ cell tumor
childhood central nervous system teratoma
childhood central nervous system yolk sac tumor
childhood astrocytoma
childhood medulloepithelioma
childhood meningioma
childhood mixed glioma
childhood oligodendroglioma
childhood pineal parenchymal tumor

Additional relevant MeSH terms:
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Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action