QUILT-3.025: A Phase 2 Study of AMG 479 in Relapsed or Refractory Ewing's Family Tumor and Desmoplastic Small Round Cell Tumors

Sponsor

NantCell, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00563680

Collaborator

(none)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	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 Design

Study Type:

Interventional

Actual Enrollment :

38 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Oct 1, 2007

Actual Primary Completion Date :

Aug 1, 2009

Actual Study Completion Date :

Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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.

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Objective response rate (Partial Response [PR] or Complete Response [CR]) as determined by RECIST [From screening to disease progression]

Secondary Outcome Measures

Assess the safety and tolerability of AMG 479 [From informed consent to the End of Study/Safety Follow-Up Visit]
Assess the duration of response [From screening to disease progression]
Assess the clinical benefit rate [From screening to disease progression]
Assess the progression free survival and overall survival [From screening to disease progression]

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)