RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. Tipifarnib may be effective in preventing the development of cancer in patients who have neurofibromatosis type 1 and plexiform neurofibromas.

PURPOSE: This randomized phase II trial is studying tipifarnib to see how well it works in preventing cancer in young patients who have neurofibromatosis type 1 and progressive plexiform neurofibromas.

OBJECTIVES:

• Determine the effect of tipifarnib on the time to disease progression in pediatric patients with neurofibromatosis type 1 and progressive plexiform neurofibromas.
• Determine the objective response rate in patients treated with this regimen.
• Determine the toxic effects of this regimen in these patients.
• Assess the quality of life of patients treated with this regimen.
• Determine the circulating levels of nerve growth factor and correlate these levels with the development of clinical neurotoxicity in patients treated with this regimen.

OUTLINE: This is a randomized, cross-over, double-blind, placebo-controlled, multicenter study. Patients are randomized to 1 of 2 arms.

• Arm I: Patients receive oral tipifarnib every 12 hours on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive oral placebo every 12 hours on days 1-21. Courses repeat as in arm I.

After documentation of disease progression, patients on both arms cross over to the other arm and (after a 2-week washout period) receive treatment as above in the absence of further disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, prior to courses 4, 7, and 10, and then after every 6 courses thereafter.

PROJECTED ACCRUAL: A total of 63 patients will be accrued for this study.

• Neurofibromatosis Type 1
• Precancerous/Nonmalignant Condition
• Sarcoma

• Drug: tipifarnib
• Other: placebo

• Experimental: Patients receive oral tipifarnib every 12 hours on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
• Placebo Comparator: Patients receive oral placebo every 12 hours on days 1-21. Courses repeat as in arm I.

DISEASE CHARACTERISTICS:

• Diagnosis of one of the following:

  • Neurofibromatosis type 1 (NF1)

  • Progressive plexiform neurofibromas

    • Neurofibromas that have grown along the length of a nerve and may involve multiple fascicles and branches (spinal neurofibromas involve 2 or more levels with connection between the levels or extending laterally along the nerve)

    • Potential to cause significant morbidity such as:

      • Head and neck lesions that could compromise airway or great vessels
      • Brachial or lumbar plexus lesions that could cause nerve compression and loss of function
      • Lesions that could result in major deformity (e.g., orbital lesions)
      • Lesions of the limb that cause limb hypertrophy or loss of function
      • Painful lesions

• Meets at least 1 other diagnostic criteria for NF1

  • 6 or more cafe-au-lait spots (at least 0.5 cm in prepubertal patients or at least 1.5 cm in postpubertal patients)
  • Freckling in the axilla or groin
  • Optic glioma
  • 2 or more Lisch nodules
  • Distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)
  • First-degree relative with NF1

• Measurable plexiform neurofibromas

  • At least 3 cm in one dimension
• Evidence of recurrent or progressive disease as documented by an increase in size or the presence of new plexiform neurofibromas on MRI
• No evidence of an optic glioma, malignant glioma, malignant peripheral nerve sheath tumor, or other cancer requiring chemotherapy or radiotherapy
• Prior surgery for progressive plexiform neurofibroma allowed provided neurofibroma was incompletely resected and is measurable
• Complete tumor resection not feasible or patient refused surgery

PATIENT CHARACTERISTICS:

Age:

• 3 to 25

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 months

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm^3
• Hemoglobin at least 9.0 g/dL
• Platelet count at least 150,000/mm^3
• Fibrinogen normal

Hepatic:

• Bilirubin normal unless due to Gilbert's syndrome
• SGPT no greater than 2 times upper limit of normal
• No significant hepatic dysfunction

Renal:

• Creatinine normal for age OR
• Creatinine clearance at least 70 mL/min

Cardiovascular:

• No significant cardiac dysfunction

Pulmonary:

• No significant pulmonary dysfunction

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No clinically significant unrelated systemic illness that would preclude study participation
• No serious infections
• No significant organ dysfunction
• No metal implanted prostheses (e.g., vascular clamps or pacemakers) that would contraindicate an MRI

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 1 week since prior filgrastim (G-CSF)
• No concurrent anticancer immunotherapy

Chemotherapy:

• See Disease Characteristics
• No more than 1 prior myelosuppressive chemotherapy regimen
• At least 4 weeks since prior chemotherapy and recovered
• No concurrent anticancer chemotherapy

Endocrine therapy:

• No concurrent anticancer hormonal therapy

Radiotherapy:

• See Disease Characteristics
• At least 6 weeks since prior radiotherapy and recovered
• No concurrent anticancer radiotherapy

Surgery:

• See Disease Characteristics

Other:

• No prior tipifarnib
• At least 30 days since prior investigational agents
• No concurrent proton pump inhibitors (e.g., omeprazole, lansoprazole, pantoprazole, rabeprazole, or esomeprazole)
• No other concurrent investigational anticancer agents