A Five-Tier, Open-Label Study of IMC-A12 in Advanced Sarcoma

Study Overview
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Brief Summary
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This multicenter study will enroll approximately 185 participants with metastatic or advanced sarcoma, to assess the effectiveness and safety of IMC-A12 monotherapy for this indication. Participants will be stratified into five tiers according to diagnosis: Ewing's sarcoma/peripheral neuroectodermal tumor (PNET) rhabdomyosarcoma leiomyosarcoma adipocytic sarcoma synovial sarcoma. A total of 85 participants will be enrolled initially, 17 in each tier. Participants will receive single agent IMC-A12 every 2 weeks. A treatment cycle will be defined as 6 weeks, with radiological evaluation at every cycle. Safety and response in the initial 17 participants in each tier will be used to determine whether to extend enrollment to the target total of 37 participants per tier.

Detailed Description
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The purpose of this study is to determine the progression-free survival (PFS) rate assessed 12 weeks after the initiation of IMC-A12 monotherapy, administered every 2 weeks to participants with previously-treated, advanced or metastatic soft tissue and Ewing's sarcoma/PNET.

Official Title
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A Five-Tier, Phase 2 Open-Label Study of IMC-A12 Administered as a Single Agent Every 2 Weeks in Patients With Previously-Treated, Advanced or Metastatic Soft Tissue and Ewing's Sarcoma/PNET

Conditions
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Ewing's Sarcoma /Peripheral Neuroectodermal Tumor (PNET), Rhabdomyosarcoma, Leiomyosarcoma, Adipocytic Sarcoma, Synovial Sarcoma

Intervention / Treatment
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* Biological: IMC-A12 (cixutumumab)
* Biological: IMC-A12 (cixutumumab)
* Biological: IMC-A12 (cixutumumab)
* Biological: IMC-A12 (cixutumumab)
* Biological: IMC-A12 (cixutumumab)


Participation Criteria
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Eligibility Criteria
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Inclusion: Histologically or cytologically-confirmed sarcoma of one of the following histologies: (1) Ewing's sarcoma / PNET; (2) rhabdomyosarcoma; (3) leiomyosarcoma; (4) adipocytic sarcoma; or (5) synovial sarcoma Has measurable disease, at least one lesion ≥ 2 centimeters (cm) on conventional measurement techniques or ≥ 1 cm on spiral computed tomography (CT) scan Has at least one measurable lesion located outside of a previously irradiated area Has radiographic documentation of disease progression within 6 months prior to study entry Has relapsed, refractory, and/or metastatic disease, incurable by surgery, radiotherapy, or other conventional systemic therapy Been considered ineligible for systemic chemotherapy or received at least one previous regimen for relapsed, refractory, and/or metastatic disease Adequate hematologic function Has adequate hepatic function Has adequate coagulation function Has adequate renal function Has fasting serum glucose < 120 milligrams per deciliter (mg/dL) or below the upper limit of normal (ULN) Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation Exclusion: Has uncontrolled brain or leptomeningeal metastases Not recovered to grade ≤ 1 from adverse events due to agents administered more than 3 weeks prior to study entry Is receiving any other investigational agent(s) Major surgery, hormonal therapy (other than replacement), chemotherapy, radiotherapy, or any form of investigational therapy within 3 weeks prior to enrollment History of treatment with other agents targeting the insulin-like growth factor-I receptor (IGF-IR) History of allergic reactions attributed to compounds of chemical or biologic composition similar to that of IMC-A12 Has poorly controlled diabetes mellitus Is receiving therapy with immunosuppressive agents Is pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMC-A12 (cixutumumab)<br> | Biological: IMC-A12 (cixutumumab)<br>* Ewing's Sarcoma/PNET 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion every two weeks. A treatment cycle will be defined as 6 weeks, with radiological evaluation at every cycle.<br>* Other names: LY3012217;Biological: IMC-A12 (cixutumumab)<br>* Rhabdomyosarcoma 10 mg/kg IV infusion every two weeks. A treatment cycle will be defined as 6 weeks, with radiological evaluation at every cycle.<br>* Other names: LY3012217;Biological: IMC-A12 (cixutumumab)<br>* Leiomyosarcoma 10 mg/kg IV infusion every two weeks. A treatment cycle will be defined as 6 weeks, with radiological evaluation at every cycle.<br>* Other names: LY3012217;Biological: IMC-A12 (cixutumumab)<br>* Adipocytic sarcoma 10 mg/kg IV infusion every two weeks. A treatment cycle will be defined as 6 weeks, with radiological evaluation at every cycle.<br>* Other names: LY3012217;Biological: IMC-A12 (cixutumumab)<br>* Synovial sarcoma 10 mg/kg IV infusion every two weeks. A treatment cycle will be defined as 6 weeks, with radiological evaluation at every cycle.<br>* Other names: LY3012217;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Progression-Free Survival (PFS) at 12 Weeks | PFS at 12 weeks was reported by disease condition and defined as the percentage of participants who have neither experienced disease progression nor died at 12 weeks after the date of first dose. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive Disease (PD) was defined as having at least a 20% increase in sum of the longest diameter of target lesions or the appearance of new lesions. Percentage of participants is calculated as the total number of participants with PFS at 12 weeks divided by the total number of participants treated then multiplied by 100. | Baseline to Disease Progression or Death Due to Any Cause Up To 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS was reported by disease condition and defined as the interval from the date of first dose until disease progression or death whichever occurred earlier. Response was defined using RECIST, version 1.0 criteria. PD was defined as having at least a 20% increase in sum of the longest diameter of target lesions or the appearance of new lesions. PFS was censored at the date of the last objective progression-free disease assessment for participants who did not experience disease progression or death. | Baseline to measured PD (up to 105.4 weeks) | 
| Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] | ORR was reported by disease condition and defined as the percentage of participants achieving either CR or PR. Response was defined using RECIST, version 1.0 criteria. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. Percentage of participants is calculated as a total number of participants with CR or PR divided by the total number of participants treated then multiplied by 100. | Baseline to measured PD (up to 105.4 weeks) | 
| Time to Response |  | Baseline to first evidence of confirmed CR or PR (up to 105.4 weeks) | 
| Duration of Response |  | Date of first response to the date of progression or death due to any cause (up to 105.4 weeks) | 
| Overall Survival (OS) | OS was reported by disease condition and defined as the duration from the date of enrollment to the date of death from any cause. For participants who were alive, OS was censored at the date of last follow-up visit or at the date of last contact. | Baseline to date of death from any cause (up to 112.9 weeks) | 
| Percentage of Participants With Best Overall Response [Clinical Benefit Rate (CBR)] | CBR was reported by disease condition. Response was defined using RECIST, version 1.0 criteria. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. Stable Disease (SD) was defined as small changes that did not meet the above criteria. Percentage of participants with best overall response is calculated as a total number of participants with CR or PR or SD divided by the total number of participants treated then multiplied by 100. | Baseline through study completion (up to 105.4 weeks) | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Deaths | TEAEs were defined as serious and other non-serious AEs that occurred or worsened after study treatment (regardless of causality). Data presented are the number of participants who experienced TEAEs, serious TEAEs, and deaths during the study including the 30-day follow-up. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Event module. | Baseline through study completion (up to 112.9 weeks) | 
| Serum Anti-IMC-A12 Antibody Assessment (Immunogenicity) |  | 30-day safety follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sarcoma, Ewing's sarcoma / peripheral neuroectodermal tumor (PNET);, rhabdomyosarcoma;, leiomyosarcoma;, adipocytic sarcoma, synovial sarcoma