Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Tipifarnib in Preventing Cancer in Children With Neurofibromatosis Type 1 and Progressive Plexiform Neurofibromas

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Prevention Active 3 to 25 NCI NCI-01-C-0222H NCI-T99-0090, NCT00029354, T99-0090

Special Category: NIH Clinical Center trial, NCI Web site featured trial

Objectives

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

Entry Criteria

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

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

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/mm³
• Hemoglobin at least 9.0 g/dL
• Platelet count at least 150,000/mm³
• 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

Expected Enrollment

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

Outcomes

Time to progression at 6 and 12 months

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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Brigitte Widemann, MD, Protocol chair		Ph: 301-496-7387

U.S.A.
Alabama
	Birmingham
	Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
		Clinical Trials Office - Lurleen Wallace Comprehensive Cancer	Ph:  205-934-0309
California
	Los Angeles
	Hospital for Sick Children
		Douglas Hyder, MD	Ph:  323-669-2121
Maryland
	Baltimore
	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
		Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Center at John Hopkins	Ph:  410-955-8804
			Email: jhcccro@jhmi.edu
	Bethesda
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
		Clinical Trials Office - Warren Grant Magnusen Clinical Center - NCI Clinical Trials Referral Office	Ph:  888-NCI-1937
Missouri
	Saint Louis
	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
		Arie Perry, MD	Ph:  314-362-7426 800-600-3606
			Email: aperry@pathbox.Wustl.edu
		David Gutmann, MD, PhD	Ph:  314-632-7379 800-600-3606
		M. Watson, MD, PhD	Ph:  314-454-7919 800-600-3606
		Michael DeBaun, MD, PhD, MPH	Ph:  314-286-1186 800-600-3606
Pennsylvania
	Philadelphia
	Children's Hospital of Philadelphia
		Jean Belasco, MD	Ph:  215-590-2800

Related Information

Featured trial article

Registry Information
Official Title		A Phase II Randomized, Cross-Over, Double-Blinded, Placebo-Controlled Trial Of The Farnesyltransferase Inhibitor R115777 In Pediatric Patients With Neurofibromatosis Type I And Progressive Plexiform Neurofibromas
Trial Start Date		2001-07-05
Trial Completion Date		2004-02-05 (estimated)
Registered in ClinicalTrials.gov		NCT00029354
Date Submitted to PDQ		2001-07-24
Information Last Verified		2005-05-05
NCI Grant/Contract Number		CM17101

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