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Melanoma (Skin)Phase 1NCT00003750

Biological Therapy in Treating Children With Refractory or Recurrent Neuroblastoma or Other Tumors

A Phase 1 study testing hu14.18-IL2 fusion protein in people with Melanoma (Skin) and Neuroblastoma, run by Children's Oncology Group at 59 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

RATIONALE: Biological therapies such as hu14.18-interleukin-2 fusion protein use different ways to stimulate the immune system and stop cancer cells from growing. PURPOSE: Phase I trial to study the effectiveness of hu14.18-interleukin-2 fusion protein in treating children who have refractory or recurrent… Read more about this study

Who is it for?
Ages Up to 21 years
Conditions the study is for
Melanoma (Skin), Neuroblastoma, Sarcoma
What is being tested?
hu14.18-IL2 fusion protein
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
59 sitesin 3 countries
Study dates
Oct 2001to Sep 2005
Phase
Phase 1
Are there results?
None posted in the registry

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 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

DISEASE CHARACTERISTICS:

  • Histologically confirmed neuroblastoma or melanoma at original diagnosis
  • Refractory to chemotherapy or recurrence after prior multiagent chemotherapy
  • Measurable or evaluable (detectable by bone scan) metastatic disease OR
  • No evidence of disease if complete response to prior surgical resection, radiotherapy, and/or chemotherapy OR
  • Histologically confirmed tumor expressing GD2 antigen at original diagnosis or relapse
  • Refractory to standard treatment
  • Measurable or evaluable disease by clinical assessments or laboratory markers OR
  • No evidence of disease after prior surgical resection of metastatic, recurrent disease
  • Histologically confirmed recurrent osteogenic sarcoma after prior chemotherapy allowed
  • Soft tissue sarcoma allowed
  • No primary CNS tumors
  • Prior CNS metastases allowed, provided:
  • Disease previously treated
  • Disease clinically stable for 4 weeks before study
  • At least 4 weeks since prior steroids for CNS metastases
  • No clinically detectable pleural effusions or ascites

PATIENT CHARACTERISTICS:

Age:

  • 21 and under

Performance status:

  • Karnofsky 60-100% for children over age 10
  • Lansky 60-100% for children age 10 and under

Life expectancy:

  • At least 12 weeks

Hematopoietic:

  • Absolute neutrophil count greater than 1,000/mm^3
  • Platelet count at least 75,000/mm^3 (transfusion allowed)
  • Hemoglobin at least 9.0 g/dL (transfusion allowed)

Hepatic:

  • Bilirubin less than 1.5 mg/dL
  • ALT or AST no greater than 2.5 times normal
  • Hepatitis B surface antigen negative

Renal:

  • Creatinine no greater than 1.5 mg/dL OR
  • Creatinine clearance or radioisotope glomerular filtration rate at least 60 mL/min

Cardiovascular:

  • Shortening fraction at least 27% by echocardiogram OR
  • Ejection fraction more than 50% by MUGA scan
  • No congestive heart failure
  • No uncontrolled cardiac rhythm disturbance

Pulmonary:

  • FEV_1 and FVC more than 60% of predicted OR
  • No dyspnea at rest
  • No exercise intolerance
  • Oxygen saturation more than 94% by pulse oximetry on room air

Neurologic:

  • No seizure disorders requiring antiseizure medications
  • No significant neurologic deficit or grade 2 or greater objective peripheral neuropathy

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative
  • No significant concurrent illnesses unrelated to cancer or its treatment
  • No significant psychiatric disabilities
  • No uncontrolled active infections
  • No uncontrolled active peptic ulcer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 1 week since prior growth factors
  • At least 1 week since prior immunomodulatory therapy
  • Prior monoclonal antibodies allowed if no detectable antibody to hu14.18
  • Prior autologous bone marrow transplantation (BMT) or stem cell transplantation (SCT) allowed
  • Prior autologous BMT or SCT with monoclonal antibody-purged specimens allowed
  • No concurrent growth factors
  • No concurrent interferon

Chemotherapy:

  • See Disease Characteristics
  • At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas, mitomycin, or melphalan)
  • No concurrent palliative chemotherapy

Endocrine therapy:

  • See Disease Characteristics
  • At least 2 weeks since prior glucocorticoids, except for life-threatening symptoms
  • No concurrent corticosteroids
  • No concurrent glucocorticoids, except for life-threatening symptoms

Radiotherapy:

  • See Disease Characteristics
  • At least 3 weeks since prior radiotherapy
  • No concurrent palliative radiotherapy

Surgery:

  • See Disease Characteristics
  • At least 2 weeks since prior major surgery (e.g., laparotomy or thoracotomy)
  • No prior organ allografts
  • No concurrent palliative surgery

Other:

  • Recovered from prior therapy
  • At least 1 week since prior tretinoin
  • At least 3 weeks since prior immunosuppressive therapy
  • No other concurrent immunosuppressive drugs

Trial locations and contacts

59 sites in 3 countries.

59 sites in 3 countries

United States54 sites

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109-0914

  • AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish RiteCampus

    Atlanta, Georgia, 30342

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21231-2410

  • Floating Hospital for Children

    Boston, Massachusetts, 02111

  • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Hollings Cancer Center at Medical University of South Carolina

    Charleston, South Carolina, 29425-0721

  • Children's Memorial Hospital - Chicago

    Chicago, Illinois, 60614

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229-3039

  • Children's Hospital of Columbus

    Columbus, Ohio, 43205-2696

  • Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas

    Dallas, Texas, 75390-9063

  • Children's Hospital of Michigan

    Detroit, Michigan, 48201

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010-3000

  • Duke Comprehensive Cancer Center

    Durham, North Carolina, 27710

  • Cook Children's Medical Center - Fort Worth

    Fort Worth, Texas, 76104

  • Shands Cancer Center at the University of Florida Health Science Center

    Gainesville, Florida, 32610-0296

  • Cancer Center at Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Texas Children's Cancer Center

    Houston, Texas, 77030-2399

  • University of Texas - MD Anderson Cancer Center

    Houston, Texas, 77030-4009

  • Indiana University Cancer Center

    Indianapolis, Indiana, 46202-5289

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216-4505

  • Kansas Cancer Institute at the University of Kansas Medical Center

    Kansas City, Kansas, 66160-7357

  • Children's Mercy Hospital

    Kansas City, Missouri, 64108

  • Rebecca and John Moores UCSD Cancer Center

    La Jolla, California, 92093-0658

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202-3591

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027-0700

  • Jonsson Comprehensive Cancer Center, UCLA

    Los Angeles, California, 90095-1781

  • University of Wisconsin Comprehensive Cancer Center

    Madison, Wisconsin, 53792-6164

  • CCOP - Marshfield Clinic Research Foundation

    Marshfield, Wisconsin, 54449

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105-2794

  • Midwest Children's Cancer Center

    Milwaukee, Wisconsin, 53226

  • University of Minnesota Cancer Center

    Minneapolis, Minnesota, 55455

  • Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center

    Nashville, Tennessee, 37232-6838

  • Robert Wood Johnson Medical School

    New Brunswick, New Jersey, 08901

  • MBCCOP - LSU Health Sciences Center

    New Orleans, Louisiana, 70112

  • NYU School of Medicine's Kaplan Comprehensive Cancer Center

    New York, New York, 10016

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10021

  • Herbert Irving Comprehensive Cancer Center at Columbia University

    New York, New York, 10032

  • Oklahoma University Medical Center at University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73126

  • Children's Hospital of Orange County

    Orange, California, 92868

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • CCOP - Columbia River Oncology Program

    Portland, Oregon, 97225

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78207

  • UCSF Comprehensive Cancer Center

    San Francisco, California, 94115

  • Children's Hospital and Regional Medical Center - Seattle

    Seattle, Washington, 98105

  • Cardinal Glennon Children's Hospital

    St Louis, Missouri, 63104

  • Washington University Medical Center

    St Louis, Missouri, 63105

  • Stanford Cancer Center at Stanford University Medical Center

    Stanford, California, 94305-5208

  • University Hospital at State University of New York - Upstate Medical University

    Syracuse, New York, 13210

  • CCOP - Scott and White Hospital

    Temple, Texas, 76508

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010-2970

Other trials in United States

Canada3 sites

  • McGill University Health Center - Montreal Children's Hospital

    Montreal, Quebec, H3G 1A4

  • Hopital Sainte Justine

    Montreal, Quebec, H3T 1C5

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

Other trials in Canada

Australia2 sites

  • Royal Children's Hospital

    Parkville, Victoria, 3052

  • Princess Margaret Hospital for Children

    Perth, Western Australia, 6001

Other trials in Australia

About this study

Official title: A Phase I/IB Intergroup Trial of the HU14.18-IL2 Fusion Protein in Children With Refractory Neuroblastoma and Other GD2 Positive Tumors

RATIONALE: Biological therapies such as hu14.18-interleukin-2 fusion protein use different ways to stimulate the immune system and stop cancer cells from growing.

PURPOSE: Phase I trial to study the effectiveness of hu14.18-interleukin-2 fusion protein in treating children who have refractory or recurrent neuroblastoma or other tumors.

Read the detailed description

OBJECTIVES:

  • Determine the maximum tolerated dose of hu14.18-interleukin-2 fusion protein in children with refractory or recurrent neuroblastoma or other GD2-positive tumors.
  • Determine the toxicity and pharmacokinetics of the fusion protein in these patients.
  • Determine the effect of the fusion protein on systemic immune modulation in these patients.
  • Quantitate the antifusion protein antibodies in patients treated with fusion protein.
  • Evaluate antitumor responses resulting from this fusion protein regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive hu14.18-interleukin-2 (hu14.18-IL2) fusion protein IV over 4 hours once daily on days 1-3. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of hu14.18-IL2 fusion protein until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 2 months for 1 year, every 6 months for 3 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 18-24 patients will be accrued for this study within 1 year.

Being tested
hu14.18-IL2 fusion protein
Keywords
metastatic osteosarcoma, recurrent neuroblastoma, recurrent osteosarcoma, recurrent melanoma, unspecified childhood solid tumor, protocol specific, metastatic childhood soft tissue sarcoma, recurrent childhood soft tissue sarcoma
Medical subject headings
Melanoma, Neuroblastoma, Sarcoma, Osteosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • hu14.18-IL2 fusion proteinBiological

Study groups in NCT00003750
Study groupRoleWhat they receive
DG2 positive relapsed or refractory solid tumorsExperimentalThe initial hu14.18-IL2 fusion protein (FP) dose will be 2 mg/m2 given intravenously over 4 hours, daily for 3 days. Five separate dose levels are scheduled: 2 mg/m²/dose (IV over 4 hours) x 3 days, 4 mg/m²/dose (IV over 4 hours) x 3 days, 6 mg/m²/dose (IV over 4 hours) x 3 days, 8 mg/m²/dose (IV over 4 hours) x 3 days, 10 mg/m²/dose (IV over 4 hours) x 3 days.
Receives: Biological: hu14.18-IL2 fusion protein

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Determine the MTD and pharmacokinetics of hu14.18-IL2 fusion protein

    Determine the MTD of hu14.18-IL2 fusion protein and determine the pharmacokinetics of the fusion protein when given as I.V. injections

Secondary outcomes (1)

  1. Assess immunological changes associated with fusion protein therapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startOct 2001
  3. Primary completionJan 2005
  4. Study completionSep 2005

Resources

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00003750
Sponsor's protocol ID
ADVL0018
Other IDs
COG-ADVL0018, CDR0000066870
Status last verified
Aug 2014
First submitted
1 Nov 1999
Last updated
8 Aug 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • Osenga KL, Hank JA, Albertini MR, Gan J, Sternberg AG, Eickhoff J, Seeger RC, Matthay KK, Reynolds CP, Twist C, Krailo M, Adamson PC, Reisfeld RA, Gillies SD, Sondel PM; Children's Oncology Group. A phase I clinical trial of the hu14.18-IL2 (EMD 273063) as a treatment for children with refractory or recurrent neuroblastoma and melanoma: a study of the Children's Oncology Group. Clin Cancer Res. 2006 Mar 15;12(6):1750-9. doi: 10.1158/1078-0432.CCR-05-2000.

    PubMed 16551859

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing hu14.18-IL2 fusion protein in people with Melanoma (Skin) and Neuroblastoma, run by Children's Oncology Group at 59 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

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 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 59 sites in United States, Canada, Australia. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Determine the MTD and pharmacokinetics of hu14.18-IL2 fusion protein. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00003750, which also lists 1 linked publication.

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 2014.

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