A Phase 2 Study of AMG 479 in Relapsed or Refractory Ewing's Family Tumor and Desmoplastic Small Round Cell Tumors - Full Text View

Sponsored by:	Amgen
Information provided by:	Amgen
ClinicalTrials.gov Identifier:	NCT00563680

Purpose

Single-arm, open-label study of AMG 479 in up to 35 subjects with Ewing's Family Tumors (EFTs) and Desmoplastic Small Round Cell Tumors (DSRCTs) who have progressed or recurred after at least one prior chemotherapy regimen.

An exploratory cohort of an additional up to 10 subjects with prior exposure to anti-IGF-1R therapy and who have progressed or recurred after at least one prior chemotherapy regimen will also be assessed.

Condition	Intervention	Phase
Askin's Tumors Desmoplastic Small Round Cell Tumors Estraosseous Ewing's Tumor Ewing's Family Tumor Ewing's Sarcoma Primitive Neuroectodermal Tumors (PNETs) Sarcoma	Drug: AMG 479	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase 2 Study of AMG 479 in Relapsed or Refractory Ewing's Family Tumor and Desmoplastic Small Round Cell Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer Soft Tissue Sarcoma

U.S. FDA Resources

Further study details as provided by Amgen:

Primary Outcome Measures:

Objective response rate (Partial Response [PR] or Complete Response [CR]) as determined by RECIST [ Time Frame: From screening to disease progression ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Assess the duration of response [ Time Frame: From screening to disease progression ] [ Designated as safety issue: No ]
Assess the clinical benefit rate [ Time Frame: From screening to disease progression ] [ Designated as safety issue: No ]
Assess the progression free survival and overall survival [ Time Frame: From screening to disease progression ] [ Designated as safety issue: No ]
Assess the safety and tolerability of AMG 479 [ Time Frame: From informed consent to the End of Study/Safety Follow-Up Visit ] [ Designated as safety issue: Yes ]

Enrollment:	38
Study Start Date:	October 2007
Estimated Study Completion Date:	January 2010
Estimated Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Exploratory Cohort: Experimental If a total of two or more responses (partial and complete) in EFTs/DSRCTs are documented in this or the ongoing phase 1 study (20050118), then the study will allow enrollment of up to 10 additional EFT/DSRCT subjects who have been exposed to prior anti-IGF-1R targeting therapy.	Drug: AMG 479 AMG 479 is a fully human monoclonal antibody (IgG1) against the insulin-like growth factor receptor-1 (IGF-1R). IGF-1R signaling has been shown to play a critical role in the survival of cancer cells. AMG 479 inhibits the binding of both IGF-1 and IGF-2 to IGF-1R, thus inhibiting ligand‑dependent receptor activation. Inhibition of IGF-1R signaling with AMG 479 provides a potential mechanism for inhibiting tumor growth and survival.
Main Cohort: Experimental Subjects with relapsed Ewing's Family Tumors (EFTs) and Desmoplastic Small Round Cell Tumors (DSRCTs) who have not received prior anti-IGF-1R therapy will receive AMG 479 at 12mg/kg.	Drug: AMG 479 AMG 479 is a fully human monoclonal antibody (IgG1) against the insulin-like growth factor receptor-1 (IGF-1R). IGF-1R signaling has been shown to play a critical role in the survival of cancer cells. AMG 479 inhibits the binding of both IGF-1 and IGF-2 to IGF-1R, thus inhibiting ligand‑dependent receptor activation. Inhibition of IGF-1R signaling with AMG 479 provides a potential mechanism for inhibiting tumor growth and survival.

Arms

Assigned Interventions

Exploratory Cohort: Experimental

If a total of two or more responses (partial and complete) in EFTs/DSRCTs are documented in this or the ongoing phase 1 study (20050118), then the study will allow enrollment of up to 10 additional EFT/DSRCT subjects who have been exposed to prior anti-IGF-1R targeting therapy.

Drug: AMG 479

AMG 479 is a fully human monoclonal antibody (IgG1) against the insulin-like growth factor receptor-1 (IGF-1R).

IGF-1R signaling has been shown to play a critical role in the survival of cancer cells. AMG 479 inhibits the binding of both IGF-1 and IGF-2 to IGF-1R, thus inhibiting ligand‑dependent receptor activation. Inhibition of IGF-1R signaling with AMG 479 provides a potential mechanism for inhibiting tumor growth and survival.

Main Cohort: Experimental

Subjects with relapsed Ewing's Family Tumors (EFTs) and Desmoplastic Small Round Cell Tumors (DSRCTs) who have not received prior anti-IGF-1R therapy will receive AMG 479 at 12mg/kg.

Drug: AMG 479

AMG 479 is a fully human monoclonal antibody (IgG1) against the insulin-like growth factor receptor-1 (IGF-1R).

IGF-1R signaling has been shown to play a critical role in the survival of cancer cells. AMG 479 inhibits the binding of both IGF-1 and IGF-2 to IGF-1R, thus inhibiting ligand‑dependent receptor activation. Inhibition of IGF-1R signaling with AMG 479 provides a potential mechanism for inhibiting tumor growth and survival.

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Male and female subjects ≥ 16 years of age with a diagnosis of EFT or DSRCT who have relapsed or progressed after at least one prior chemotherapeutic regimen will be eligible for this study.

Before any study-specific procedure, the appropriate written informed consent must be obtained.

Inclusion Criteria:

Disease Related Subjects with pathological or histological diagnosis of Ewing's Family Tumor or Desmoplastic Small Round Cell Tumor.

Measurable disease as defined by RECIST.
Documented failure of at least one prior chemotherapy regimen for their disease.
Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.

Demographic

Males or females ≥ 16 years old.
Signed written informed consent.
Able to comply with visits and procedures.

Laboratory

Willing to provide existing and/or newly acquired tumor samples.
Diabetic Subjects (Type 1 or 2) must have HgbA1c < 8.0% and fasting blood glucose level < 160 mg/dL.

General

Must be willing and able to use birth control (double barrier protection or abstinence) during and for 6 months after the study
Prior exposure to another anti-IGF-1R therapy will only be allowed for a limited number of additional subjects (up to 10) in an exploratory cohort

Exclusion Criteria

Disease Related

Known brain metastasis.
History of bleeding diathesis.
History of another malignancy.
History of chronic hepatitis.
Documented prior history of human immunodeficiency virus.

Laboratory

Absolute neutrophil count < 1.5 x109/L.
Platelet count < 100 x 109/L.
Hemoglobin < 9 g/dL.
PT > 1.5 x institutional upper limit of normal (IULN) or PTT > 1.0 x IULN.
Serum creatinine > 1.5 x IULN.
Aspartate aminotransferase (AST) > 2.5 x IULN or Alanine aminotransferase (ALT) > 2.5 x IULN (> 5.0 x if liver metastases present).
Total bilirubin > 1.5 IULN (> 3.0 x with documented Gilbert's Syndrome)

Medication

Antitumor treatment within 21 days of Study Day 1.
Anticoagulation therapy within 28 days of Study Day 1.
Major surgery within 28 days of Study Day 1.

General

Other investigational procedures are excluded.
Inability to tolerate intravenous administration.
Subject is pregnant (eg, positive HCG test) or is breast feeding.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00563680

Locations

United States, California
Research Site
Los Angeles, California, United States
United States, Florida
Research Site
Miami, Florida, United States
United States, Illinois
Research Site
Chicago, Illinois, United States
United States, Massachusetts
Research Site
Boston, Massachusetts, United States
United States, North Carolina
Research Site
Winston-Salem, North Carolina, United States
United States, Ohio
Research Site
Cincinnati, Ohio, United States
United States, Texas
Research Site
San Antonio, Texas, United States
United States, Utah
Research Site
Salt Lake VALUE, Utah, United States
Australia
Research Site
Parkville, Australia
Canada, Alberta
Research Site
Edmonton, Alberta, Canada
Canada, Ontario
Research Site
Hamilton, Ontario, Canada
Canada, Quebec
Research Site
Montreal, Quebec, Canada

Sponsors and Collaborators

Amgen

Investigators

Study Director:

MD

Amgen

More Information

Additional Information:

AmgenTrials clinical trials website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Amgen Inc. ( Global Development Leader )
Study ID Numbers:	20060283
Study First Received:	November 21, 2007
Last Updated:	August 20, 2009
ClinicalTrials.gov Identifier:	NCT00563680 History of Changes
Health Authority:	Australia: Therapeutic Goods Administration; Canada: Health Products and Food Branch; Canada: Institutional Review Board; United States: Food and Drug Administration; United States: Institutional Review Board; Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Amgen:

AMG 479
IGF-1R
Insulin-like growth factor

Insulin-like growth factor receptor
Ewing's
Sarcoma

Study placed in the following topic categories:

Desmoplastic Small Round Cell Tumor
Neuroectodermal Tumors, Primitive
Osteosarcoma
Ewing's Sarcoma
Insulin
Antibodies, Monoclonal
Neuroectodermal Tumors
Neoplasms, Connective and Soft Tissue
Antibodies
Sarcoma, Ewing's

Malignant Mesenchymal Tumor
Soft Tissue Sarcomas
Neoplasms, Germ Cell and Embryonal
Sarcoma
Mitogens
Osteogenic Sarcoma
Neuroepithelioma
Ewing's Family of Tumors
Immunoglobulins
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neuroectodermal Tumors, Primitive
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Osteosarcoma
Neoplasms, Connective and Soft Tissue
Neuroectodermal Tumors
Sarcoma, Ewing's

Neoplasms
Neoplasms, Bone Tissue
Neoplasms, Germ Cell and Embryonal
Sarcoma
Neoplasms, Connective Tissue
Neoplasms, Neuroepithelial
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on September 10, 2009