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Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal TumorPhase 1NCT00609141

IMC-A12 in Treating Young Patients With Relapsed or Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor or Other Solid Tumor

A Phase 1 study testing cixutumumab, pharmacological study and laboratory biomarker analysis in people with Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor and Unspecified Childhood Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 1 site in United States.

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

This phase I clinical trial is studying the side effects and best dose of IMC-A12 in treating young patients with relapsed or refractory Ewing sarcoma/peripheral primitive neuroectodermal tumor or other solid tumors. Monoclonal antibodies, such as IMC-A12, can block cancer growth in different ways. Read more about this study

Who is it for?
Ages 1 year to 21 years
What is being tested?
cixutumumab, pharmacological study and laboratory biomarker analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
1 siteUnited States
Study dates
Jan 2008to Sep 2009
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 1 year to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Histologically confirmed solid tumor
  • Relapsed or refractory disease
  • No central nervous system (CNS) tumor or lymphoma
  • Histological confirmation may have been made at original diagnosis or at relapse
  • Current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
  • Measurable or evaluable disease
Show all 49Show fewer
  • Patients with Ewing sarcoma/peripheral primitive neuroectodermal tumor (PNET) must have tissue blocks or slides available
  • Study chair must be notified if tissue blocks or slides are not available
  • Karnofsky performance status (PS) ≥ 50% (patients > 10 years of age) and Lansky (PS) ≥ 50% (patients ≤ 10 years of age)
  • Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
  • Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age/gender as follows:
  • 1 to < 2 years (males and females 0.6 mg/dL)
  • 2 to < 6 years (males and females 0.8 mg/dL)
  • 6 to < 10 years (males and females 1.0 mg/dL)
  • 10 to < 13 years (males and females 1.2 mg/dL)
  • 13 to < 16 years (males 1.5 mg/dL and females 1.4 mg/dL)
  • ≥ 16 years (males 1.7 mg/dL and females 1.4 mg/dL)
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
  • SGPT (ALT) ≤ 110 μ/L (for the purpose of this study, the ULN for SGPT is 45 μ/L)
  • Serum albumin ≥ 2 g/dL
  • Patients with known bone marrow metastatic disease will be eligible for study but not evaluable for hematologic toxicity
  • Patients must not be known to be refractory to red cell or platelet transfusion
  • Patients with solid tumors without bone marrow involvement must meet the following criteria:
  • Peripheral absolute neutrophil count ≥ 1,000/μL
  • Platelet count ≥ 100,000/μL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
  • Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study therapy
  • No uncontrolled infection
  • No known type I or type II diabetes mellitus
  • Able to comply with the safety monitoring requirements of the study, in the opinion of the investigator
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to IMC-A12
  • Fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
  • At least 7 days since prior and no concurrent hematopoietic growth factors
  • Growth factors that support platelet or white cell number or function can only be administered for culture-proven bacteremia or invasive fungal infection
  • At least 7 days since prior and no concurrent biologic antineoplastic agents
  • At least 6 weeks since prior monoclonal antibodies
  • At least 3 months since prior total body irradiation (TBI), craniospinal external radiotherapy (XRT), or ≥ 50% radiotherapy to the pelvis
  • At least 2 weeks since prior local XRT (small port)
  • At least 6 weeks since other prior substantial bone marrow radiotherapy
  • More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea)
  • More than 7 days since prior and no concurrent systemic corticosteroids
  • Prior stem cell transplant or rescue allowed provided there has been no evidence of active graft-versus-host-disease within the past 2 months
  • No prior monoclonal antibody therapy targeting the IGF-IR
  • No concurrent chemotherapy, radiotherapy, or immunotherapy
  • No concurrent anticancer agents
  • No concurrent insulin or growth hormone therapy
  • No other concurrent investigational drugs

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • COG Phase I Consortium

    Arcadia, California, 91006-3776

Other trials in United States

About this study

Official title: A Phase I Study of IMC-A12 (Anti-IGF-I Receptor Monoclonal Antibody, NSC #742460) in Children With Relapsed/Refractory Solid Tumors

This phase I clinical trial is studying the side effects and best dose of IMC-A12 in treating young patients with relapsed or refractory Ewing sarcoma/peripheral primitive neuroectodermal tumor or other solid tumors. Monoclonal antibodies, such as IMC-A12, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate the maximum tolerated dose (MTD) or recommended phase II dose of IMC-A12 (cixutumumab) in children with relapsed or refractory solid tumors using a limited dose-escalation strategy.

II. To define and describe the toxicities of this drug in children with relapsed or refractory solid tumors.

III. To characterize the pharmacokinetics of this drug in children with relapsed or refractory solid tumors.

SECONDARY OBJECTIVES:

  1. To preliminarily define the antitumor activity of this drug in children with relapsed or refractory solid tumors within the confines of a phase I study.

II. To obtain initial phase II efficacy data on the antitumor activity of this drug in children with Ewing sarcoma/peripheral primitive neuroectodermal tumor (PNET).

III. To examine change in IGF-IR and insulin receptor (IR) levels and IGF-IR and IR activation in lymphocytes as biomarkers of IMC-A12 action and specificity.

IV. To evaluate the effect of this drug on circulating levels of proteins involved in linear growth and glucose homeostasis, including IGF-I, IGF-II, IGF-BP3, growth hormone, insulin, and C-peptide.

  1. To develop exploratory data concerning biomarkers of activity.

OUTLINE: This is a dose-escalation study.

Patients receive cixutumumab IV over 1 hour on days 1, 8, 15, and 22. Treatment repeats every 4 weeks for up to 2 years in the absence of unacceptable toxicity or disease progression.

Patients undergo blood sample collection periodically for pharmacokinetic, immunogenicity, and other correlative studies. Samples are analyzed for serum levels of IGF-I, IGF-II, IGF-BP3, growth hormone, insulin, and C-peptide; trough concentrations and PK sampling; and biomarkers, including IGF-IR expression and phosphorylation and insulin receptor expression and phosphorylation via immunoprecipitation and Western immunoblotting. Tumor tissue samples from patients with Ewing sarcoma/peripheral PNET are banked for future research.

After completion of study treatment, patients are followed at 30 days.

Being tested
cixutumumab, pharmacological study, laboratory biomarker analysis
Medical subject headings
Neuroectodermal Tumors, Primitive, Peripheral

What participants receive

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

  • cixutumumabBiological

    Also called anti-IGF-1R recombinant monoclonal antibody IMC-A12, IMC-A12

    Given IV

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00609141
Study groupRoleWhat they receive
Treatment (monoclonal antibody therapy)ExperimentalPatients receive cixutumumab IV over 1 hour on days 1, 8, 15, and 22. Treatment repeats every 4 weeks for up to 2 years in the absence of unacceptable toxicity or disease progression.
Receives: Biological: cixutumumab; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

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

  1. Adverse events as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0

    Toxicity tables will be constructed to summarize the observed incidence by severity and type of toxicity.

    Measured: Weekly during each course

  2. MTD or recommended phase II dose

    MTD will be the maximum dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT). DLT is defined as any hematological and non-hematological toxicities that is possible, probably, or definitely attributed to IMC-A12.

    Measured: During course 1

  3. Pharmacokinetics of IMC-A12

    Measured: At baseline, days 1, 8, 15, 22, and 28 of course 1, and days 15 and 28 of course 2

Secondary outcomes (1)

  1. Response rate (complete or partial response) in patients with Ewing sarcoma/peripheral PNET

    Confidence intervals will be constructed according to the method of Chang and O'Brien to account for the two-stage design.

    Measured: Up to 30 days after completion of treatment

Timeline

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

  1. First posted6 Feb 2008 (estimated)
  2. Study startJan 2008
  3. Primary completionSep 2009

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
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00609141
Sponsor's protocol ID
NCI-2009-00363
Other IDs
NCI-2009-00363, COG-ADVL0712, CDR0000585700, ADVL0712, ADVL0712, U01CA097452
Status last verified
Jun 2014
First submitted
2 Feb 2008
Last updated
19 Jun 2014
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing cixutumumab, pharmacological study and laboratory biomarker analysis in people with Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor and Unspecified Childhood Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) 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 49 inclusion and 0 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 19 Jun 2014. 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 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?

Adverse events as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (time frame: Weekly during each course). The study lists 3 primary outcomes in all. 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 NCT00609141.

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 19 Jun 2014.

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