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Interferon Alfa-2b |
Intron A |
Clinical Trial: A Phase I Trial of Peginterferon alfa-2b (PEG-Intron) for Plexiform Neurofibromas
This study is currently recruiting patients.
Verified by National Institutes of Health Clinical Center (CC) August 30, 2005
Purpose
NF1 is a common autosomal dominant, progressive neurogenetic disorder characterized by diverse, progressive cutaneous, neurological, skeletal and neoplastic manifestations with no standard drug treatment options available. Plexiform neurofibromas (PNs) are benign nerve sheath tumors that may cause severe morbidity and even mortality. Alpha-interferon has resulted in clinical improvement and radiographic stability without objective responses in patients with plexiform neurofibromas. The pegylated form of interferon (PEG-Intron) significantly prolongs its plasma half-life, and thereby provides protracted activity. The PEG Intron will be given as a subcutaneous injection weekly as an outpatient. Parents will be taught to administer the drug. Response will be assessed clinically and radiographically using volumetric analysis performed at the NCI.
Treatment with PEG Intron will continue for two years unless there is evidence of disease progression, unacceptable toxicity, or the subject requests that therapy be discontinued. Tolerability of the study treatment will be assessed from clinical observation, routine laboratory testing, over the course of therapy. Following completion of therapy, subjects will continue to be followed for evidence of tumor progression.
| Intervention | Phase |
|---|---|
| Drug: Peginterferon Alfa-2b (PEG-Intron) | Phase I |
MedlinePlus consumer health information
Study Type: Interventional
Study Design: Treatment, Safety
Further Study Details:
Expected Total Enrollment: 36
Study start: September 2, 2005
NF1 is a common autosomal dominant, progressive neurogenetic disorder characterized by diverse, progressive cutaneous, neurological, skeletal and neoplastic manifestations with no standard drug treatment options available. Plexiform neurofibromas (PNs) are benign nerve sheath tumors that may cause severe morbidity and even mortality. Alpha-interferon has resulted in clinical improvement and radiographic stability without objective responses in patients with plexiform neurofibromas. The pegylated form of interferon (PEG-Intron) significantly prolongs its plasma half-life, and thereby provides protracted activity. The PEG Intron will be given as a subcutaneous injection weekly as an outpatient. Parents will be taught to administer the drug. Response will be assessed clinically and radiographically using volumetric analysis performed at the NCI.
Treatment with PEG Intron will continue for two years unless there is evidence of disease progression, unacceptable toxicity, or the subject requests that therapy be discontinued. Tolerability of the study treatment will be assessed from clinical observation, routine laboratory testing, over the course of therapy. Following completion of therapy, subjects will continue to be followed for evidence of tumor progression.
Eligibility
Genders Eligible for Study: Both
Criteria
INCLUSION CRITERIA
-Age: greater than or equal to 18 months to 21 years of age
-Diagnosis: Progressive, symptomatic (i.e. interfering with performance status) or life-threatening plexiform neurofibroma 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 should be biopsied prior to therapy. Patients without biopsy-proof of a plexiform neurofibroma must have at least one other diagnostic criteria for NF1 as defined by the NIH Consensus Conference:
1. Six or more cafe-au-lait spots (greater than 0.5 cm in prepubertal subjects or greater than 1.5 cm in postpubertal subjects)
2. Freckling in the axilla or groin
3. Optic glioma
4. Two or more Lisch nodules
5. A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)
6. A first degree relative with NF1
-Patients who do not meet the diagnostic criteria for NF1 must have a biopsy proven plexiform neurofibroma to be eligible.
- Surgery/Residual disease: Patients are only eligible if complete tumor resection is not feasible, or if a patient with a surgical option refuses surgery. Patients must be at least 21 days from surgery, if performed, prior to receiving their first dose of study drug. Patients must have residual tumor present, as assessed by the surgeon and/or imaging, if surgery has been performed. Evidence of recurrent or progressive disease is NOT necessary.
- Prior therapy: Since there is no standard effective chemotherapy for patients with progressive plexiform neurofibromas, patients may be treated on this trial without having received prior therapy. If patients have received prior therapy, they must have recovered from all toxic effects prior to entering this study.
- Performance Status: Patients should have a life expectancy of at least 12 months and an ECOG performance score of 0, 1, or 2 (see below). Patients who are wheelchair bound because of paralysis should be considered "ambulatory" when they are up in their wheel chair.
ECOG Performance Status
1. Score 0:Clinical Status Asymptomatic
2. Score 1: Clinical Status Symptomatic, fully ambulatory
3. Score 2: Clincial Status Symptomatic, in bed less than 50 percent of the day
4. Score 3: Clinical Status Symptomatic, in bed greater than 50 percent of the day but not bedridden
5. Score 4: Clinical Status Bedridden
-Organ Function: Subjects must have adequate hepatic, renal and bone marrow function as defined by the following parameters:
1. An absolute granulocyte count greater than 1500/microliter, a hemoglobin greater than 10 gm/dl, and a platelet count greater than 100,000/microliter at study entry.
3. An age-adjusted normal serum creatinine (see table below) OR a creatinine clearance greater than or equal to 70 mL/min/1.73 m(2) .
Ages less than or equal to 5 and Maximum Serum Creatinine level of .8 mg/dl
Ages 5 to 10 and Maximum Serum Creatinine level of 1.0 mg/dl
Ages 10 to 15 and Maximum Serum Creatinine level of 1.2 mg/dl
Ages greater than 15 and Maximum Serum Creatinine level of 1.5 mg/dl
The above studies must be obtained within 28 days prior to study entry. If surgery is performed, the studies must be obtained AFTER surgery.
- Informed Consent: All patients or their legal guardians (if the patients is less than 18 years old) must sign an IRB approved document of informed consent indicating their understanding of the investigational nature and the risks of this study BEFORE any protocol related studies are performed (this does not include routine laboratory tests or imaging studies required to establish eligibility). When appropriate, pediatric patients will be included in all discussion in order to obtain verbal assent.
EXCLUSION CRITERIA
- Clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) which in the judgment of the Principal or Associate Investigator would compromise the patient''''s ability to tolerate PEG Intron or are likely to interfere with the study procedures or results.
- An investigational agent within the past 30 days
- Evidence of active visual pathway glioma
- History of malignant peripheral nerve sheath tumor or other cancer other than surgically cured non-melanoma skin cancer or cervical carcinoma in situ
- 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
- Severe cardiovascular disease, i.e., arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease
- Pre-existing severe psychiatric condition or a history of a psychiatric disorder requiring hospitalization or a history of suicidal ideation or attempt
- Thyroid dysfunction not responsive to therapy
- Uncontrolled diabetes mellitus
- History of seropositivity for HIV
- Subjects who are pregnant, lactating, or of reproductive potential and not practicing an effective means of contraception
- Subjects who are known to be actively abusing alcohol or drugs
- Subjects who have not recovered from the effects of recent surgery
Location and Contact Information
Please refer to this study by ClinicalTrials.gov identifier NCT00156754
Maryland
National Cancer Institute (NCI), 9000 Rockville Pike, Bethesda, Maryland, 20892, United States; Recruiting
Patient Recruitment and Public Liaison Office 1-800-411-1222 prpl@mail.cc.nih.gov
TTY 1-866-411-1010
TTY 1-866-411-1010
More Information
Detailed Web Page
Publications
Goldberg Y, Dibbern K, Klein J, Riccardi VM, Graham JM Jr. Neurofibromatosis type 1--an update and review for the primary pediatrician. Clin Pediatr (Phila). 1996 Nov;35(11):545-61. Review.
Hajdu SI. Peripheral nerve sheath tumors. Histogenesis, classification, and prognosis. Cancer. 1993 Dec 15;72(12):3549-52. No abstract available.
Huson SM, Harper PS, Compston DA. Von Recklinghausen neurofibromatosis. A clinical and population study in south-east Wales. Brain. 1988 Dec;111 ( Pt 6):1355-81.
Study ID Numbers: 050232; 05-C-0232
Last Updated: September 9, 2005
Record first received: September 9, 2005
ClinicalTrials.gov Identifier: NCT00156754
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-09-13
Last Updated: September 9, 2005
Record first received: September 9, 2005
ClinicalTrials.gov Identifier: NCT00156754
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-09-13
Resources
- Interferon Alfa-2b (Drug Digest)
- Intron A (Drug Digest)
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