Sorafenib in Children and Young Adults With Recurrent or Progressive Low-Grade Astrocytomas

NCT01338857 | Terminated Phase 2 Results DMC

• 1 other identifier: 10-00561
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if a drug called sorafenib can shrink LGA tumors (low-grade astrocytomas) in children and adults. Previous research has given us a better understanding of this type of tumor by studying the genetic "make-up" of LGAs. From this research, the investigators found that a drug called sorafenib may stop the growth of tumor cells by blocking some of the molecules needed for cell growth and by blocking blood flow to the tumor. This trial is studying how well sorafenib works in treating patients with LGAs, and how the effects relate to the specific genetic "make-up" of your particular tumor. This testing of your tumor's genetic make-up is optional and requires available tumor tissue for testing. In summary, the aims of this study are: To see if sorafenib can shrink LGAs; how well sorafenib is tolerated in patients with LGAs; and, how the effects of sorafenib relate to the genetic make-up of individual LGAs (Optional Study)

Conditions

neurofibromatosis1 (NF1); Recurrent or Progressive Optic Pathway Gliomas (OPG); Recurrent or Progressive Low-grade Glioma

Keywords

neurofibromatosis1 (NF1); Recurrent or progressive optic pathway gliomas (OPG); Recurrent or progressive low-grade glioma; sorafenib; low-grade astrocytoma

Outcome Measures

Primary Outcomes (2)

• Response Rate to Sorafenib

  To estimate the objective response rates to sorafenib in children and young adults with low-grade astrocytomas, including optic pathway gliomas.

  one year

• Objective Response Rates

  Determination of tumor response (CR, PR, SD) will be defined based on the comparison of the baseline MRI performed at study entry to the subsequent MRI which demonstrated best response. PR will be defined by a \>15% decrease in tumor volume, as measured by 3D volumetric analysis.

  MRIs performed after every 3rd 28-day cycle and off-study

Study Arms (1)

Sorafenib (Nexavar)

EXPERIMENTAL

Sorafenib will be administered orally BID (approximately every 12 hours). Grapefruit juice is not allowed while taking sorafenib. A cycle of therapy is considered to be 28 days and there is no interruption between cycles. Patients may receive up to a total of 12 cycles provided that no off-protocol or off-study criteria are met.

Drug: Sorafenib (Nexavar)

Interventions

Sorafenib (Nexavar) DRUG

Sorafenib (in tablet form) will be administered orally BID (approximately every 12 hours). Grapefruit juice is not allowed while taking sorafenib. A cycle of therapy is considered to be 28 days and there is no interruption between cycles. Patients may receive up to a total of 12 cycles provided that no off-protocol or off-study criteria are met. Children/adolescents (\< 18 years of age, non-NF1): 200 mg/m2/dose PO twice daily (rounded to the nearest 50 mg increment as per Section 4.1) to a maximum of 400 mg PO twice daily Adults (greater than or equal to 18 years of age, non-NF1): 400 mg PO twice daily NF1 patients (regardless of age): 80 mg/m2/dose PO twice daily (rounded to the nearest 50 mg increment as per Section 4.1) to a maximum of 150 mg PO twice daily

Sorafenib (Nexavar)

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: greater than or equal to 2 years of age
• Patients with neurofibromatosis-1 (NF1) are eligible
• Recurrent/progressive optic pathway gliomas (OPG) by MRI criteria, after standard therapy - histologic confirmation not required OR Histologically confirmed, radiographically recurrent or progressive low-grade glioma (WHO grade I or II) by MRI criteria, after standard therapy.
• Karnofsky performance status (PS) 60-100% (greater than or equal to 16 years of age) OR Lansky PS 60-100% (\< 16 years of age)
• Absolute neutrophil count ≥ 1,000/mm³ (unsupported)
• Platelet count ≥ 75,000/mm³ (unsupported)
• Normal PT, PTT, and INR (for patients on prophylactic anticoagulation only)
• Diastolic blood pressure (DBP) ≤ the 95th percentile for age and gender and not currently receiving medication for the treatment of hypertension.
• Adequate pulmonary function, defined as: no evidence of dyspnea at rest, no exercise intolerance, and pulse oximetry \> 94% if termination is clinically indicated.
• Not received myelosuppressive chemotherapy or treatment with biologicals or monoclonal antibodies within 4 weeks of enrollment onto this study (6 weeks if prior nitrosurea)
• At least 7 days since the completion of therapy with a hematopoietic growth factor and at least 14 days from the last administration of PEGylated GCSF (Neulasta®)
• If prior radiation therapy, ≥ 6 months must have elapsed since the last fraction for craniospinal therapy and ≥ 3 months for focal radiotherapy including radiosurgery.
• If prior surgery, ≥ 8 weeks must have elapsed since (≥ 4 weeks for minor surgery/procedures including central line placement)
• Steroids are allowed for progressive symptoms but patient must be on a stable or decreasing dose for at least 1 week prior to study entry
• Any neurologic deficits must be stable for ≥ 1 week

You may not qualify if:

• Patients with serious concurrent infection or medical illness, including overt hepatic or renal disease, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety.
• Baseline hypertension greater than grade 1.
• Prior treatment with sorafenib
• Other concurrent investigational drugs
• Other concurrent anticancer agents or therapies, including chemotherapy, radiotherapy, immunotherapy, or biologic therapy
• Concurrent therapeutic anticoagulation. Prophylactic anticoagulation (i.e. low dose heparin) of venous or arterial access devices is allowed.
• Concurrent administration of any of cytochrome P450 enzyme-inducing agents, including grapefruit juice and drugs listed under Section 9.7.
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• Uncontrolled hypertension Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
• Active clinically serious infection
• Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
• Pulmonary hemorrhage/bleeding event
• Any other hemorrhage/bleeding event
• Serious non-healing wound, ulcer, or bone fracture.
• Evidence or history of unresolved bleeding diathesis or coagulopathy.

Sponsors & Collaborators

• NYU Langone Health: lead
• Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma: collaborator

Study Sites (1)

New York University Stephen D. Hassenfeld Children's Center for Cancer & Blood Disorders

New York, New York, 10016, United States

Location

Related Publications (1)

• Legault G, Kieran MW, Scott RM, Chordas C, Milla SS, Karajannis MA. Recurrent ascites in a patient with low-grade astrocytoma and ventriculo-peritoneal shunt treated with the multikinase inhibitor sorafenib. J Pediatr Hematol Oncol. 2014 Nov;36(8):e533-5. doi: 10.1097/MPH.0000000000000094.

  PMID: 24351969 DERIVED

MeSH Terms

Conditions

Recurrence

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Matthias A. Karajannis, MD
• Organization: New York University Langone Medical Center

matthias.karajannis@nyumc.org

212-263-9630

Study Officials

• Matthias A Karajannis, MD

  NYU

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2011
• First Posted: April 20, 2011
• Study Start: April 1, 2011
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: February 17, 2017
• Results First Posted: February 22, 2016

Record last verified: 2016-12

Locations

US (1)