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

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ClinicalTrials.gov Identifier: NCT00668148
Recruitment Status : Completed
First Posted : April 29, 2008
Results First Posted : July 17, 2018
Last Update Posted : July 17, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

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:

  1. Ewing's sarcoma/peripheral neuroectodermal tumor (PNET)
  2. rhabdomyosarcoma
  3. leiomyosarcoma
  4. adipocytic sarcoma
  5. 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.


Condition or disease Intervention/treatment Phase
Ewing's Sarcoma /Peripheral Neuroectodermal Tumor (PNET) Rhabdomyosarcoma Leiomyosarcoma Adipocytic Sarcoma Synovial Sarcoma Biological: IMC-A12 (cixutumumab) Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 113 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : July 2008
Actual Primary Completion Date : October 2010
Actual Study Completion Date : February 2012


Arm Intervention/treatment
Experimental: IMC-A12 (cixutumumab) Biological: IMC-A12 (cixutumumab)

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.

Other Names:
  • cixutumumab
  • LY3012217

Biological: IMC-A12 (cixutumumab)

Rhabdomyosarcoma

10 mg/kg IV infusion every two weeks.

A treatment cycle will be defined as 6 weeks, with radiological evaluation at every cycle.

Other Names:
  • cixutumumab
  • LY3012217

Biological: IMC-A12 (cixutumumab)

Leiomyosarcoma

10 mg/kg IV infusion every two weeks.

A treatment cycle will be defined as 6 weeks, with radiological evaluation at every cycle.

Other Names:
  • cixutumumab
  • LY3012217

Biological: IMC-A12 (cixutumumab)

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.

Other Names:
  • cixutumumab
  • LY3012217

Biological: IMC-A12 (cixutumumab)

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.

Other Names:
  • cixutumumab
  • LY3012217




Primary Outcome Measures :
  1. Percentage of Participants With Progression-Free Survival (PFS) at 12 Weeks [ Time Frame: Baseline to Disease Progression or Death Due to Any Cause Up To 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 :
  1. Progression-Free Survival (PFS) [ Time Frame: Baseline to measured PD (up to 105.4 weeks) ]
    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.

  2. Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] [ Time Frame: Baseline to measured PD (up to 105.4 weeks) ]
    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.

  3. Time to Response [ Time Frame: Baseline to first evidence of confirmed CR or PR (up to 105.4 weeks) ]
  4. 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) ]
  5. Overall Survival (OS) [ Time Frame: Baseline to date of death from any cause (up to 112.9 weeks) ]
    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.

  6. Percentage of Participants With Best Overall Response [Clinical Benefit Rate (CBR)] [ Time Frame: Baseline through study completion (up to 105.4 weeks) ]
    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.

  7. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Deaths [ Time Frame: Baseline through study completion (up to 112.9 weeks) ]
    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.

  8. Serum Anti-IMC-A12 Antibody Assessment (Immunogenicity) [ Time Frame: 30-day safety follow-up ]


Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00668148


Locations
United States, Colorado
ImClone Investigational Site
Aurora, Colorado, United States, 80045
United States, Florida
ImClone Investigational Site
Orlando, Florida, United States, 32806
United States, Louisiana
ImClone Investigational Site
Metairie, Louisiana, United States, 70006-2921
ImClone Investigational Site
Metairie, Louisiana, United States, 70006
United States, Michigan
ImClone Investigational Site
Detroit, Michigan, United States, 48201-2014
United States, Missouri
ImClone Investigational Site
Saint Louis, Missouri, United States, 63110
United States, Ohio
ImClone Investigational Site
Columbus, Ohio, United States, 43210
Belgium
ImClone Investigational Site
Brussels, Belgium, 1000
ImClone Investigational Site
Leuven, Belgium, 3000
ImClone Investigational Site
Wilrijk, Belgium, 2610
France
ImClone Investigational Site
Bordeaux, France, 33076
ImClone Investigational Site
Lyon, France, 69008
ImClone Investigational Site
Paris, France, 75231
ImClone Investigational Site
Toulouse, France, 31052
Germany
ImClone Investigational Site
Dresden, Germany, 01307
ImClone Investigational Site
Mannheim, Germany, 68167
Netherlands
ImClone Investigational Site
Leiden, Netherlands, 2333 ZA
Poland
ImClone Investigational Site
Warsaw, Poland, 02-781
Spain
ImClone Investigational Site
Barcelona, Spain, 08025
ImClone Investigational Site
Barcelona, Spain, 08035
ImClone Investigational Site
Barcelona, Spain, 08041
ImClone Investigational Site
Barcelona, Spain, 08907
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: E-mail: ClinicalTrials@ ImClone.com ImClone LLC

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00668148     History of Changes
Other Study ID Numbers: 13925
2007-006719-21 ( EudraCT Number )
CP13-0707 ( Other Identifier: ImClone, LLC )
I5A-IE-JAEC ( Other Identifier: Eli Lilly and Company )
First Posted: April 29, 2008    Key Record Dates
Results First Posted: July 17, 2018
Last Update Posted: July 17, 2018
Last Verified: June 2018

Keywords provided by Eli Lilly and Company:
Sarcoma
Ewing's sarcoma / peripheral neuroectodermal tumor (PNET);
rhabdomyosarcoma;
leiomyosarcoma;
adipocytic sarcoma
synovial sarcoma

Additional relevant MeSH terms:
Sarcoma
Sarcoma, Ewing
Sarcoma, Synovial
Rhabdomyosarcoma
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Leiomyosarcoma
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Myosarcoma
Neoplasms, Muscle Tissue
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neoplasms, Glandular and Epithelial
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs