Study of PEG-Intron for Plexiform Neurofibromas

NCT00396019 | Completed Phase 2 Results DMC

• 1 other identifier: UPCI 06-116
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

Brief Summary

This study is for slow growing tumors called plexiform neurofibromas (PNF) which are a relatively common problem in people with neurofibromatosis type 1 (NF1). These tumors are benign but as they grow, they can become disfiguring as well as disabling or even life threatening. They often cause pain, difficulty using arms or legs because of spinal cord compression, and/or nerve damage. At present, the only available therapy for plexiform neurofibromas is to try to surgically remove as much of the tumor as is possible. Because these tumors grow into the surrounding areas, total surgical resection is often impossible. Most tumors will re-grow after surgery if the entire tumor cannot be removed. To date, other treatments including chemotherapy and radiotherapy have not been able to shrink these tumors. Interferon is a drug that is used for different types of tumors as well as for hepatitis. It has been used in the treatment of plexiform neurofibromas (PNF) with some subjects showing improvement in symptoms and/or a decrease in the size of the tumor. Most subjects had no further growth of their tumor while on the PEG-Intron. The drug used in this study is PEG (pegylated)-Intron. PEG-Intron is a long acting form of interferon which keeps the drug from being broken down in the body for a longer period of time and potentially could be more effective than the short-acting interferon. PEG-Intron has been approved by the Food and Drug Administration (FDA) for the treatment of Hepatitis C. The goals of this study are:

1. 1.To determine how your child's plexiform neurofibroma responds to PEG-Intron when given weekly.
2. 2.To determine the side effects of PEG-Intron when given weekly to participants with plexiform neurofibromas.
3. 3.To evaluate a new method of measuring changes in the size of tumors called volume analysis. This method measures the entire volume of a tumor in three dimensions. The standard method of measuring tumors uses only the length and/or width of the tumor. By studying the different ways of measuring tumors the investigators hope to be able to determine which method is the most accurate and useful.

Conditions

Plexiform Neurofibroma

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Imaging Response in Strata 1 and 2

  A response was defined as a ≥20% reduction in the sum of the volume of the "target" plexiform neurofibroma ( PN) within 12 months confirmed by a follow-up MRI after ≥4 weeks.

  MRI scans were performed at baseline and at months 4, 8, 12, 18, and 24 while on treatment and every 6 months thereafter until off study.

• Clinical Response in Stratum 2

  Clinical response was defined as a protocol-specified improvement in ophthalmologic evaluation, an improvement of at least one level in performance status (PS) ≥50% decrease in the amount of pain medications required per week compared with baseline or ability to change from a narcotic to a nonnarcotic analgesic, sustained for at least one month.

  baseline, week 6, months 4, 8, 12, 18, and 24 while on treatment and every 6 months thereafter until off study

• Time to Progression (TTP) in Stratum 3

  TTP was estimated by the Kaplan-Meter method

  baseline, week 6, months 4, 8, 12, 18, and 24 while on treatment and every 6 months thereafter until off study

Secondary Outcomes (1)

• Number of Participants With Imaging Response in Stratum 3

  MRI scans were performed at baseline and at months 4, 8, 12, 18, and 24 while on treatment and every 6 months thereafter until off study

Interventions

PEG-Intron DRUG

Eligibility Criteria

• Age: 18 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age \> or equal to 18 months to 21 years
• Diagnosis Patients with NF1 and progressive, symptomatic or life-threatening plexiform neurofibromas which are not surgically resectable. Patients without biopsy-proof of plexiform must have at least one other diagnostic criteria for NF1: 6 or more cafe-au-lait spots, freckling in the axilla or groin, optic glioma, 2 or more Lisch nodules, distinctive bony lesion, first degree relative with NF1.
• Only eligible if complete tumor resection is not feasible, or if a patient with a surgical option refuses surgery.
• 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.
• Must have life expectancy of at least 12 months and a performance score (Karnofsky or Lansky) of \> or equal to 50.
• Must have adequate liver, kidney and bone marrow function

You may not qualify if:

• Clinically significant unrelated systemic illness.
• Received an investigational agent within the past 30 days.
• Evidence of active visual pathway glioma
• History of malignant peripheral nerve sheath tumor or ther 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
• Severe cardiovascular disease
• Pre-existing sever psychiatric condition or history of 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.
• Any medical condition requiring chronic systemic corticosteroids.
• Subjects who are known to be actively abusing alcohol or drugs.

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Related Publications (1)

• Jakacki RI, Dombi E, Steinberg SM, Goldman S, Kieran MW, Ullrich NJ, Pollack IF, Goodwin A, Manley PE, Fangusaro J, Allen R, Widemann BC. Phase II trial of pegylated interferon alfa-2b in young patients with neurofibromatosis type 1 and unresectable plexiform neurofibromas. Neuro Oncol. 2017 Feb 1;19(2):289-297. doi: 10.1093/neuonc/now158.

  PMID: 27510726 RESULT

MeSH Terms

Conditions

Neurofibroma, Plexiform

Interventions

peginterferon alfa-2b

Condition Hierarchy (Ancestors)

Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases

Results Point of Contact

• Title: Dr. Regina Jakacki
• Organization: AstraZeneca

regina.jakacki@astrazeneca.com

Study Officials

• Jean Tersak, M.D.

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Study Record Dates

• First Submitted: November 2, 2006
• First Posted: November 6, 2006
• Study Start: December 1, 2006
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: November 6, 2017
• Results First Posted: November 6, 2017

Record last verified: 2017-10

Locations

US (1)