Combination Chemotherapy in Treating Patients With Neurofibromatosis and Progressive Plexiform Neurofibromas

NCT00030264 | Completed Phase 2 Results DMC

• 2 other identifiers: 07-2339CHP-686
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

Neurofibromatosis Type 1; Precancerous Condition

Keywords

plexiform neurofibroma; neurofibromatosis type 1

Outcome Measures

Primary Outcomes (1)

• Time to Disease Progression

  Disease progression was assessed both radiographically and clinically. Tumor assessments to assess for radiographic disease progression were assessed by magnetic resonance imaging (MRI) measurement whenever possible or computed tomography (CT) scan and/or tumor measurement during physical examination of palpable lesions. Clinical assessments for clinical progression of disease were assessed by treating physician or designee. Progressive disease as measured by the appearance of new lesions; an increased size of index tumor(s) by \>/= 25% of the sum of the products of baseline measurements; and/or by increase in symptoms.

  6 months

Study Arms (1)

Methotrexate & Vinblastine

EXPERIMENTAL

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; Drug: Vinblastine

Interventions

Methotrexate 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)

Methotrexate & Vinblastine

Vinblastine 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.

Methotrexate & Vinblastine

Eligibility Criteria

• Age: Up to 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• 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
• 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
• 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
• 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.

You may not qualify if:

• 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.
• A Pregnancy test must be negative for females of childbearing age.
• 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.
• Pregnant females are excluded
• Patient has had treatment with an investigational agent within the past 30 days.
• Ongoing radiation therapy, chemotherapy, hormonal therapy directed at the tumor or immunotherapy.
• Inability to return for follow-up visits or obtain follow-up studies required to assess toxicity and response to therapy.

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Neurofibromatosis 1; Precancerous Conditions; Neurofibroma, Plexiform

Interventions

Methotrexate; Vinblastine

Condition Hierarchy (Ancestors)

Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Peripheral Nervous System Neoplasms; Nervous System Neoplasms

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Results Point of Contact

• Title: Ratnakar Patti
• Organization: Children's Hospital of Philadelphia

267-426-5503

Study Officials

• Jean B. Belasco, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2002
• First Posted: January 27, 2003
• Study Start: February 1, 2001
• Primary Completion: December 1, 2013
• Study Completion: March 1, 2016
• Last Updated: August 8, 2018
• Results First Posted: August 8, 2018

Record last verified: 2018-07

Locations

US (1)