A Five-Tier, Open-Label Study of IMC-A12 in Advanced Sarcoma
Condition: Ewing's Sarcoma /Peripheral Neuroectodermal Tumor (PNET); Rhabdomyosarcoma; Leiomyosarcoma; Adipocytic Sarcoma; Synovial Sarcoma
MeSH terms: Sarcoma; Rhabdomyosarcoma; Sarcoma, Ewing; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Leiomyosarcoma; Sarcoma, Synovial; Neuroectodermal Tumors, Primitive, Peripheral
Intervention: IMC-A12 (cixutumumab); IMC-A12 (cixutumumab); IMC-A12 (cixutumumab); IMC-A12 (cixutumumab); IMC-A12 (cixutumumab)
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.; Rhabdomyosarcoma
10 mg/kg IV infusion every two weeks.
A treatment cycle will be defined as 6 weeks, with radiological evaluation at every cycle.; Leiomyosarcoma
10 mg/kg IV infusion every two weeks.
A treatment cycle will be defined as 6 weeks, with radiological evaluation at every cycle.; 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.; 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.
Intervention MeSH terms: Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 113.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: Sarcoma; Ewing's sarcoma / peripheral neuroectodermal tumor (PNET);; rhabdomyosarcoma;; leiomyosarcoma;; adipocytic sarcoma; synovial sarcoma

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.
    

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