Combination Chemotherapy in Treating Patients With Neurofibromatosis and Progressive Plexiform Neurofibromas

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Brief Title

Combination Chemotherapy in Treating Patients With Neurofibromatosis and Progressive Plexiform Neurofibromas

Official Title

Vinblastine/Methotrexate For Severe Progressive Plexiform Neurofibromas: A Phase II Study

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Time to Disease Progression


Condition

Neurofibromatosis Type 1

Intervention

Methotrexate

Study Arms / Comparison Groups

 Methotrexate & Vinblastine
Description:  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).

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

23

Start Date

February 2001

Completion Date

March 2016

Primary Completion Date

December 2013

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.

          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.
      

Gender

All

Ages

N/A - 25 Years

Accepts Healthy Volunteers

No

Contacts

Jean B. Belasco, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00030264

Organization ID

07-2339

Secondary IDs

CHP-686

Responsible Party

Sponsor

Study Sponsor

Children's Hospital of Philadelphia


Study Sponsor

Jean B. Belasco, MD, Principal Investigator, Children's Hospital of Philadelphia


Verification Date

July 2018