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

NCT01158300 | Completed Phase 1 DMC

• 4 other identifiers: CDR0000680634U01CA081457PBTC-031PTC299-ONC-010-PBT
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 8

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Maximum-tolerated dose

  First four weeks of treatment

• Adverse events

  From the first day of treatment until 30 days after the last dose

Secondary Outcomes (3)

• Percentage of study participants with complete response or partial response to the study treatment

  Every 8 weeks

• Pharmacokinetics

  Day 1 and day 28 of course 1

• Change from baseline in blood angiogenic markers and cytokines at discontinuation or completion of treatment

  Before the first dose of drug on day 1 of course 1 and at the discontinuation or completion of treatment

Interventions

VEGF inhibitor PTC299 DRUG

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)

Eligibility Criteria

• Age: 3 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * 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 PATIENT CHARACTERISTICS: * 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 PRIOR CONCURRENT THERAPY: * 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Pediatric Brain Tumor Consortium: lead
• National Cancer Institute (NCI): collaborator
• PTC Therapeutics: collaborator

Study Sites (8)

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, 94143-0128, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4318, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital

Houston, Texas, 77030-2399, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Astrocytoma; Familial ependymoma; Medulloblastoma; Spinal Cord Neoplasms; Optic Nerve Glioma; Meningioma; Oligodendroglioma

Interventions

emvododstat

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Spinal Cord Diseases; Central Nervous System Diseases; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Diseases; Optic Nerve Diseases; Eye Diseases; Neoplasms, Vascular Tissue; Meningeal Neoplasms

Study Officials

• Roger J. Packer, MD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2010
• First Posted: July 8, 2010
• Study Start: November 1, 2010
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: May 4, 2015

Record last verified: 2015-05

Locations

US (8)