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Phase I and Pharmacokinetic Trial of PTC299 in Pediatric Patients With Refractory or Recurrent CNS Tumors

Phase 1
3 Years
21 Years
Not Enrolling
Brain and Central Nervous System Tumors

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Trial Information

Phase I and Pharmacokinetic Trial of PTC299 in Pediatric Patients With Refractory or Recurrent CNS Tumors



- 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

- 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

- 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.

Inclusion Criteria


- 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

- 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

- 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

- At least 3 weeks since prior myelosuppressive anticancer chemotherapy (6 weeks for

- At least 14 days since prior investigational or biological agent

- At least 3 half-lives since prior biological agents that have a prolonged

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum-tolerated dose

Outcome Time Frame:

First four weeks of treatment

Safety Issue:


Principal Investigator

Roger J. Packer, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

November 2010

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • 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
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms



Children's Hospital of Philadelphia Philadelphia, Pennsylvania  19104
Duke Comprehensive Cancer Center Durham, North Carolina  27710
UCSF Cancer Center and Cancer Research Institute San Francisco, California  94115-0128
Children's National Medical Center Washington, District of Columbia  20010-2970
Children's Hospital of Pittsburgh Pittsburgh, Pennsylvania  15213
Children's Memorial Hospital - Chicago Chicago, Illinois  60614
St. Jude Children's Research Hospital Memphis, Tennessee  38105-2794
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital Houston, Texas  77030-2399