Combination Chemotherapy in Treating Patients With Neurofibromatosis and Progressive Plexiform Neurofibromas

NCT ID: NCT00030264

Last Updated: 2018-08-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-02-28
• Study Completion Date: 2016-03-31

Brief Summary

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.

Detailed Description

OBJECTIVES:

• 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.

Conditions

Neurofibromatosis Type 1; Precancerous Condition

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Methotrexate

Intervention Type: DRUG

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)

Vinblastine

Intervention Type: DRUG

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.

Interventions

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)

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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.

Exclusion Criteria

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.

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.

• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital of Philadelphia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean B. Belasco, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

CHP-686

Identifier Type: OTHER

Identifier Source: secondary_id

07-2339

Identifier Type: -

Identifier Source: org_study_id