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

Phase 2

Completed

• Conditions: Ewing's Sarcoma; Primitive Neuroectodermal Tumors (PNETs); Sarcoma; Askin's Tumors; Desmoplastic Small Round Cell Tumors; Estraosseous Ewing's Tumor; Ewing's Family Tumor
• Interventions: Drug: AMG 479

• Registration Number: NCT00563680
• Lead Sponsor: NantCell, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2007-10
• Study First Submitted: 2007-11-21
• Study First Submitted QC: 2007-11-21
• Study First Posted: 2007-11-26
• Primary Completion: 2009-08
• Study Completion: 2012-08
• Disposition First Submitted: 2015-01-16
• Disposition First Submitted QC: 2015-01-16
• Disposition First Posted: 2015-01-28
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-26
• Last Update Posted: 2016-10-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 38

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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Exploratory Cohort	AMG 479	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.
Main Cohort	AMG 479	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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