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

Study Overview
=================
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.

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

Conditions
-----------------
Askin's Tumors, Desmoplastic Small Round Cell Tumors, Estraosseous Ewing's Tumor, Ewing's Family Tumor, Ewing's Sarcoma, Primitive Neuroectodermal Tumors (PNETs), Sarcoma

Intervention / Treatment
-----------------
* Drug: AMG 479


Participation Criteria
=================
Eligibility 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.

Ages Eligible for Study
-----------------
Minimum Age: 16 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exploratory Cohort<br>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<br>* 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.<br>|
| Experimental: Main Cohort<br>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<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (Partial Response [PR] or Complete Response [CR]) as determined by RECIST |  | From screening to disease progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
AMG 479, IGF-1R, Insulin-like growth factor, Insulin-like growth factor receptor, Ewing's, Sarcoma