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

Primary Purpose

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

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
IMC-A12 (cixutumumab)
IMC-A12 (cixutumumab)
IMC-A12 (cixutumumab)
IMC-A12 (cixutumumab)
IMC-A12 (cixutumumab)
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ewing's Sarcoma /Peripheral Neuroectodermal Tumor (PNET) focused on measuring Sarcoma, Ewing's sarcoma / peripheral neuroectodermal tumor (PNET);, rhabdomyosarcoma;, leiomyosarcoma;, adipocytic sarcoma, synovial sarcoma

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

IMC-A12 (cixutumumab)

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
Time to Response
Duration of Response
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.
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.
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.
Serum Anti-IMC-A12 Antibody Assessment (Immunogenicity)

Full Information

First Posted
April 25, 2008
Last Updated
June 18, 2018
Sponsor
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT00668148
Brief Title
A Five-Tier, Open-Label Study of IMC-A12 in Advanced Sarcoma
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
July 2008 (undefined)
Primary Completion Date
October 2010 (Actual)
Study Completion Date
February 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ewing's Sarcoma /Peripheral Neuroectodermal Tumor (PNET), Rhabdomyosarcoma, Leiomyosarcoma, Adipocytic Sarcoma, Synovial Sarcoma
Keywords
Sarcoma, Ewing's sarcoma / peripheral neuroectodermal tumor (PNET);, rhabdomyosarcoma;, leiomyosarcoma;, adipocytic sarcoma, synovial sarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
113 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IMC-A12 (cixutumumab)
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
IMC-A12 (cixutumumab)
Other Intervention Name(s)
cixutumumab, LY3012217
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
IMC-A12 (cixutumumab)
Other Intervention Name(s)
cixutumumab, LY3012217
Intervention Description
Rhabdomyosarcoma 10 mg/kg IV infusion every two weeks. A treatment cycle will be defined as 6 weeks, with radiological evaluation at every cycle.
Intervention Type
Biological
Intervention Name(s)
IMC-A12 (cixutumumab)
Other Intervention Name(s)
cixutumumab, LY3012217
Intervention Description
Leiomyosarcoma 10 mg/kg IV infusion every two weeks. A treatment cycle will be defined as 6 weeks, with radiological evaluation at every cycle.
Intervention Type
Biological
Intervention Name(s)
IMC-A12 (cixutumumab)
Other Intervention Name(s)
cixutumumab, LY3012217
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
IMC-A12 (cixutumumab)
Other Intervention Name(s)
cixutumumab, LY3012217
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Participants With Progression-Free Survival (PFS) at 12 Weeks
Description
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.
Time Frame
Baseline to Disease Progression or Death Due to Any Cause Up To 12 Weeks
Secondary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
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.
Time Frame
Baseline to measured PD (up to 105.4 weeks)
Title
Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
Description
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.
Time Frame
Baseline to measured PD (up to 105.4 weeks)
Title
Time to Response
Time Frame
Baseline to first evidence of confirmed CR or PR (up to 105.4 weeks)
Title
Duration of Response
Time Frame
Date of first response to the date of progression or death due to any cause (up to 105.4 weeks)
Title
Overall Survival (OS)
Description
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.
Time Frame
Baseline to date of death from any cause (up to 112.9 weeks)
Title
Percentage of Participants With Best Overall Response [Clinical Benefit Rate (CBR)]
Description
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.
Time Frame
Baseline through study completion (up to 105.4 weeks)
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Deaths
Description
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.
Time Frame
Baseline through study completion (up to 112.9 weeks)
Title
Serum Anti-IMC-A12 Antibody Assessment (Immunogenicity)
Time Frame
30-day safety follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
E-mail: ClinicalTrials@ ImClone.com
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
ImClone Investigational Site
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
ImClone Investigational Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
ImClone Investigational Site
City
Metairie
State/Province
Louisiana
ZIP/Postal Code
70006-2921
Country
United States
Facility Name
ImClone Investigational Site
City
Metairie
State/Province
Louisiana
ZIP/Postal Code
70006
Country
United States
Facility Name
ImClone Investigational Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201-2014
Country
United States
Facility Name
ImClone Investigational Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
ImClone Investigational Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
ImClone Investigational Site
City
Brussels
ZIP/Postal Code
1000
Country
Belgium
Facility Name
ImClone Investigational Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
ImClone Investigational Site
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
Facility Name
ImClone Investigational Site
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
ImClone Investigational Site
City
Lyon
ZIP/Postal Code
69008
Country
France
Facility Name
ImClone Investigational Site
City
Paris
ZIP/Postal Code
75231
Country
France
Facility Name
ImClone Investigational Site
City
Toulouse
ZIP/Postal Code
31052
Country
France
Facility Name
ImClone Investigational Site
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
ImClone Investigational Site
City
Mannheim
ZIP/Postal Code
68167
Country
Germany
Facility Name
ImClone Investigational Site
City
Leiden
ZIP/Postal Code
2333 ZA
Country
Netherlands
Facility Name
ImClone Investigational Site
City
Warsaw
ZIP/Postal Code
02-781
Country
Poland
Facility Name
ImClone Investigational Site
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
Facility Name
ImClone Investigational Site
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
ImClone Investigational Site
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
ImClone Investigational Site
City
Barcelona
ZIP/Postal Code
08907
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
22682017
Citation
Asmane I, Watkin E, Alberti L, Duc A, Marec-Berard P, Ray-Coquard I, Cassier P, Decouvelaere AV, Ranchere D, Kurtz JE, Bergerat JP, Blay JY. Insulin-like growth factor type 1 receptor (IGF-1R) exclusive nuclear staining: a predictive biomarker for IGF-1R monoclonal antibody (Ab) therapy in sarcomas. Eur J Cancer. 2012 Nov;48(16):3027-35. doi: 10.1016/j.ejca.2012.05.009. Epub 2012 Jun 7.
Results Reference
derived

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

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