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

• Status: Terminated
• Trial end date: 2013-03-01
• Target enrollment: 0
• Participant gender: All

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)

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: New York University School of Medicine; NYU Langone Health
• Collaborator: Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
• Treatments: Niacinamide; Sorafenib

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

• Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.

• Known or suspected allergy to sorafenib.

• Any malabsorption problem.

• Patients with history of any prior CNS bleeding.

• Patients with any non-healed wounds.