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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00563680
First received: November 21, 2007
Last updated: June 5, 2014
Last verified: June 2014
  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 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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:


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 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 ]
  • 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 ]

Enrollment: 38
Study Start Date: October 2007
Study Completion Date: August 2012
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exploratory Cohort
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.
Experimental: Main Cohort
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00563680     History of Changes
Other Study ID Numbers: 20060283
Study First Received: November 21, 2007
Last Updated: June 5, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
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

Keywords provided by Amgen:
AMG 479
IGF-1R
Insulin-like growth factor
Insulin-like growth factor receptor
Ewing's
Sarcoma

Additional relevant MeSH terms:
Desmoplastic Small Round Cell Tumor
Neoplasms
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Sarcoma
Sarcoma, Ewing
Neoplasms by Histologic Type
Neoplasms, Bone Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms, Connective Tissue
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Osteosarcoma
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 23, 2014