Combination Chemotherapy in Treating Patients With Neurofibromatosis and Progressive Plexiform Neurofibromas

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Children's Hospital of Philadelphia Identifier:
First received: February 14, 2002
Last updated: September 30, 2015
Last verified: September 2015

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining methotrexate with vinblastine may be effective treatment for neurofibromatosis type 1 associated with progressive plexiform neurofibromas.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients who have neurofibromatosis type 1 associated with progressive plexiform neurofibromas.

Condition Intervention Phase
Neurofibromatosis Type 1
Precancerous Condition
Drug: Methotrexate
Drug: Vinblastine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Vinblastine/Methotrexate For Severe Progressive Plexiform Neurofibromas: A Phase II Study

Resource links provided by NLM:

Further study details as provided by Children's Hospital of Philadelphia:

Primary Outcome Measures:
  • Time to disease progression [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Tumor response will be assessed by magnetic resonance imaging (MRI) measurement whenever possible or computed tomography (CT) scan and/or tumor measurement during physical examination of palpable lesions.

Enrollment: 25
Study Start Date: February 2001
Estimated Study Completion Date: December 2015
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Methotrexate & Vinblastine
Methotrexate and Vinblastine will be given once a week for the first 26 weeks and then every two weeks for the next 26 weeks or until disease progression (whichever occurs first).
Drug: Methotrexate
Methotrexate will be given at a dose of 30mg/m2/week intramuscular (IM) or intravenous (IV) for the first 26 weeks, then every 2 weeks for the next 26 weeks or until disease progression (whichever occurs first)
Drug: Vinblastine
Vinblastine will be given at a dose of 6mg/m2/week intravenous (IV) for for the first 26 weeks, then every 2 weeks for the next 26 weeks or until disease progression (whichever occurs first). Maximum actual dose may not exceed 10mg.

Detailed Description:


  • Determine the effect of chronic vinblastine and methotrexate on time to disease progression in children or young adults with progressive plexiform neurofibroma associated with neurofibromatosis type 1.
  • Determine the objective response rate in patients treated with this regimen.
  • Determine the toxic effects of this regimen in these patients.
  • Determine the quality of life of patients treated with this regimen.

OUTLINE: Patients are stratified according to tumor status (severely debilitating and/or life-threatening vs cosmetically disfiguring).

Patients receive methotrexate and vinblastine IV weekly for 26 weeks and then every 2 weeks for 26 weeks in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and then every 3 months during study participation.

Patients are followed every 3 months until disease progression.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study within approximately 3 years.


Ages Eligible for Study:   up to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Progressive, debilitating, severely disfiguring or life-threatening plexiform neurofibroma (PN) which is not surgically resectable and for which there is no other standard medical management. Histologic confirmation of tumor is not required in the presence of consistent clinical and radiographic findings. However, if any clinical observation or scan suggests possible malignant transformation, the tumor must be biopsied prior to therapy. In addition to PN, all study subjects must have at least one other diagnostic criteria for Neurofibromatosis type 1 (NF1) listed below:

    • 6 or more café-au-lait spots > 0.5 cm in prepubertal subjects or > 1.5 cm in postpubertal subjects
    • freckling in the axilla or groin
    • optic glioma
    • 2 or more lisch nodules
    • a distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)
    • a first degree relative with NF1
  2. Adequate bone marrow, renal, hepatic function:

    • Absolute Neutrophil Count (ANC)> 1000 and platelet count >100,000 prior to initiation of therapy
    • must have normal renal function: Blood Urea Nitrogen (BUN)/Creatinine <1.5x normal for age), alkaline phosphatase (ALP), albumin, total protein and bilirubin
    • must have normal liver function: Bilirubin, alanine transaminase (ALT), aspartate aminotransferase (AST) < 1.5x normal for age
  3. Patients must have measurable PN by direct physical examination (documented by clinical measurement of tumor and serial photography) or by imaging studies. Most patients will have tumors that can be measured by magnetic resonance imaging (MRI), however, some patients may have cosmetically disfiguring PN which would be best measured clinically and with serial photography throughout treatment and follow-up. A measurable lesion is one whose size can be quantified in at least 2 dimensions. There must be evidence of recurrent or progressive disease as documented by an increase in size or the presence of new lesions on MRI. Progression is defined as the appearance of new tumors or a measurable increase in the sum of the product of the two longest perpendicular diameters of the index lesion(s) over a time period < 12 months prior to evaluation for this study. For purposes of this study, index PN lesions will be those PNs evaluated as the most life-threatening, debilitating, cosmetically disfiguring, and/or most easily measured.
  4. Prior therapy: Patients with NF1 are eligible at the time of recurrence or progression of inoperable PN. A surgical consultation should be obtained prior to enrollment on the study to evaluate if tumor resection is a feasible option. Patients will only be eligible if complete tumor resection is not feasible or if a patient with a surgical option refuses surgery. Since there is no standard effective chemotherapy for patients with NF1 and progressive PN, patients may be treated on this trial without having received prior therapy. Patients must have recovered from the toxic effects of all prior therapy before entering this study. The Cancer Therapy Evaluation Program Common Toxicity Criteria (CTC) Version 2.0 will be used for toxicity assessment. Recovery is defined as a toxicity grade < 2, unless otherwise specified in the Inclusion and Exclusion Criteria. Patients must have had their last dose of radiation therapy at least 6 weeks prior to study entry, and their last dose of chemotherapy at least four weeks prior to study entry. Patients who received granulocyte-colony stimulating factor (G-CSF) after the prior cycle of chemotherapy must be off G-CSF for at least one week prior to entering this study.
  5. Performance status: Patients should have a life expectancy of at least 12 months and a Lansky or Karnofsky performance score of > 60. Patients who are wheelchair bound because of paralysis should be considered "ambulatory" when they are mobile and active in their wheelchairs rather than actually ambulatory.
  6. A Pregnancy test must be negative for females of childbearing age.
  7. Informed consent: All patients or their legal guardians (if the patient is less than 18 years old) must sign an approved document of informed consent indicating their understanding of the investigational nature and the risks of this study before beginning therapy. When appropriate pediatric patients will be included in all discussion in order to obtain verbal assent.

Exclusion Criteria:

  1. Pregnant females are excluded
  2. Patient has had treatment with an investigational agent within the past 30 days.
  3. Ongoing radiation therapy, chemotherapy, hormonal therapy directed at the tumor or immunotherapy.
  4. Inability to return for follow-up visits or obtain follow-up studies required to assess toxicity and response to therapy.
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Please refer to this study by its identifier: NCT00030264

United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Children's Hospital of Philadelphia
Principal Investigator: Jean B. Belasco, MD Children's Hospital of Philadelphia
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Hospital of Philadelphia Identifier: NCT00030264     History of Changes
Other Study ID Numbers: 07-2339, CHP-686
Study First Received: February 14, 2002
Last Updated: September 30, 2015
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Children's Hospital of Philadelphia:
plexiform neurofibroma
neurofibromatosis type 1

Additional relevant MeSH terms:
Nerve Sheath Neoplasms
Neurofibroma, Plexiform
Neurofibromatosis 1
Precancerous Conditions
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplastic Syndromes, Hereditary
Nervous System Diseases
Nervous System Neoplasms
Neurocutaneous Syndromes
Neurodegenerative Diseases
Neuromuscular Diseases
Peripheral Nervous System Diseases
Peripheral Nervous System Neoplasms
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Dermatologic Agents processed this record on October 06, 2015