Sorafenib in Children and Young Adults With Recurrent or Progressive Low-Grade Astrocytomas
Condition: neurofibromatosis1 (NF1); Recurrent or Progressive Optic Pathway Gliomas (OPG); Recurrent or Progressive Low-grade Glioma
MeSH terms: Glioma; Astrocytoma; Neurofibromatoses; Neurofibromatosis 1; Neurofibroma; Recurrence
Intervention: Sorafenib (Nexavar)
Intervention description: 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
Intervention MeSH terms: Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 2 Years
Healthy volunteers: No
Keywords: neurofibromatosis1 (NF1); Recurrent or progressive optic pathway gliomas (OPG); Recurrent or progressive low-grade glioma; sorafenib; low-grade astrocytoma

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)
    

Eligibility 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.