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

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

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.

Study Overview

• Status: Completed
• Conditions: Leiomyosarcoma; Rhabdomyosarcoma; Synovial Sarcoma; Ewing's Sarcoma /Peripheral Neuroectodermal Tumor (PNET); Adipocytic Sarcoma
• Intervention / Treatment: Biological: IMC-A12 (cixutumumab); Biological: IMC-A12 (cixutumumab); Biological: IMC-A12 (cixutumumab); Biological: IMC-A12 (cixutumumab); Biological: IMC-A12 (cixutumumab)

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
• Enrollment (Actual): 113
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • ImClone Investigational Site
  • Leuven, Belgium, 3000
    • ImClone Investigational Site
  • Wilrijk, Belgium, 2610
    • ImClone Investigational Site
• France
  • Bordeaux, France, 33076
    • ImClone Investigational Site
  • Lyon, France, 69008
    • ImClone Investigational Site
  • Paris, France, 75231
    • ImClone Investigational Site
  • Toulouse, France, 31052
    • ImClone Investigational Site
• Germany
  • Dresden, Germany, 01307
    • ImClone Investigational Site
  • Mannheim, Germany, 68167
    • ImClone Investigational Site
• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • ImClone Investigational Site
• Poland
  • Warsaw, Poland, 02-781
    • ImClone Investigational Site
• Spain
  • Barcelona, Spain, 08035
    • ImClone Investigational Site
  • Barcelona, Spain, 08025
    • ImClone Investigational Site
  • Barcelona, Spain, 08041
    • ImClone Investigational Site
  • Barcelona, Spain, 08907
    • ImClone Investigational Site
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • ImClone Investigational Site
  • Florida
    • Orlando, Florida, United States, 32806
      • ImClone Investigational Site
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • ImClone Investigational Site
    • Metairie, Louisiana, United States, 70006-2921
      • ImClone Investigational Site
  • Michigan
    • Detroit, Michigan, United States, 48201-2014
      • ImClone Investigational Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • ImClone Investigational Site
  • Ohio
    • Columbus, Ohio, United States, 43210
      • ImClone Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: LY3012217; cixutumumab; 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: LY3012217; cixutumumab; 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: LY3012217; cixutumumab; 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: LY3012217; cixutumumab; 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: LY3012217; cixutumumab

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: E-mail: ClinicalTrials@ ImClone.com, Eli Lilly and Company

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: April 25, 2008
• First Submitted That Met QC Criteria: April 28, 2008
• First Posted (Estimate): April 29, 2008

Study Record Updates

• Last Update Posted (Actual): July 17, 2018
• Last Update Submitted That Met QC Criteria: June 18, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Sarcoma; synovial sarcoma; Ewing's sarcoma / peripheral neuroectodermal tumor (PNET);; rhabdomyosarcoma;; leiomyosarcoma;; adipocytic sarcoma
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Muscle Tissue; Myosarcoma; Sarcoma; Sarcoma, Ewing; Leiomyosarcoma; Rhabdomyosarcoma; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Sarcoma, Synovial; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• 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)