Know Cancer

or
forgot password

A Phase I Study of IMC-A12 (Anti-IGF-I Receptor Monoclonal Antibody, IND #100947, NSC #742460) in Children With Relapsed/Refractory Solid Tumors


Phase 1
1 Year
21 Years
Not Enrolling
Both
Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Unspecified Childhood Solid Tumor, Protocol Specific

Thank you

Trial Information

A Phase I Study of IMC-A12 (Anti-IGF-I Receptor Monoclonal Antibody, IND #100947, NSC #742460) in Children With Relapsed/Refractory Solid Tumors


PRIMARY OBJECTIVES:

I. 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:

I. 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.

V. 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.


Inclusion Criteria:



- 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

- 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Description:

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

Outcome Time Frame:

Weekly during each course

Safety Issue:

Yes

Principal Investigator

Suman Malempati

Investigator Role:

Principal Investigator

Investigator Affiliation:

COG Phase I Consortium

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00363

NCT ID:

NCT00609141

Start Date:

January 2008

Completion Date:

Related Keywords:

  • Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
  • Unspecified Childhood Solid Tumor, Protocol Specific
  • Neuroectodermal Tumors
  • Neuroectodermal Tumors, Primitive
  • Neoplasms
  • Sarcoma, Ewing's
  • Neuroectodermal Tumors, Primitive, Peripheral
  • Sarcoma

Name

Location

COG Phase I ConsortiumArcadia, California  91006-3776