Neurofibromatosis Type 1Phase 2NCT00030264
Combination Chemotherapy in Treating Patients With Neurofibromatosis and Progressive Plexiform Neurofibromas
A Phase 2 study testing Methotrexate and Vinblastine in people with Neurofibromatosis Type 1 and Precancerous Condition, run by Children's Hospital of Philadelphia at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 25 years
- Conditions the study is for
- Neurofibromatosis Type 1, Precancerous Condition
- What is being tested?
- Methotrexate and Vinblastine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2001to Mar 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
Show all 16Show fewer
- 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.
- 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.
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: Vinblastine/Methotrexate For Severe Progressive Plexiform Neurofibromas: A Phase II Study
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.
Read the 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
- Being tested
- Methotrexate, Vinblastine
- Keywords
- plexiform neurofibroma, neurofibromatosis type 1
- Medical subject headings
- Neurofibromatosis 1, Precancerous Conditions, Neurofibroma, Plexiform
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
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)
VinblastineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Methotrexate; Drug: Vinblastine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startFeb 2001
- Primary completionDec 2013
- Study completionMar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neurofibromatosis Type 1Studies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jean B. Belasco, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00030264
- Sponsor's protocol ID
- 07-2339
- Other IDs
- CHP-686
- Status last verified
- Jul 2018
- First submitted
- 14 Feb 2002
- Last updated
- 8 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vinblastine/Methotrexate For Severe Progressive Plexiform Neurofibromas: A Phase II Study
- ClinicalTrials.gov ID
- NCT00030264
- Acronym / sponsor ID
- 07-2339
- Conditions
- Neurofibromatosis Type 1, Precancerous Condition
- Keywords
- plexiform neurofibroma, neurofibromatosis type 1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Study start
- Feb 2001
- Primary completion
- Dec 2013 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Posted 8 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Methotrexate & Vinblastine | Experimental | Drug: Methotrexate, Drug: VinblastineMethotrexate 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). |
Who may qualify
- Ages
- Up to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (16 listed)
- 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:
- Adequate bone marrow, renal, hepatic function:
- 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.
- 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.
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethotrexateMethotrexate 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 | Methotrexate & Vinblastine |
| VinblastineVinblastine 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. | Drug | Methotrexate & Vinblastine |
Primary outcome
Time to Disease Progression
Time frame: 6 months
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean B. Belasco, MD principal investigator
Children's Hospital of Philadelphia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Methotrexate and Vinblastine in people with Neurofibromatosis Type 1 and Precancerous Condition, run by Children's Hospital of Philadelphia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Disease Progression (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2018.