Clinical trial NCT00668148: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2008-04-29
Enrollment: 113
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

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

Primary outcomes:
measure: Percentage of Participants With Progression-Free Survival (PFS) at 12 Weeks
timeFrame: Baseline to Disease Progression or Death Due to Any Cause Up To 12 Weeks
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Baseline to measured PD (up to 105.4 weeks)
measure: Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
timeFrame: Baseline to measured PD (up to 105.4 weeks)
measure: Time to Response
timeFrame: Baseline to first evidence of confirmed CR or PR (up to 105.4 weeks)
measure: Duration of Response
timeFrame: Date of first response to the date of progression or death due to any cause (up to 105.4 weeks)
measure: Overall Survival (OS)
timeFrame: Baseline to date of death from any cause (up to 112.9 weeks)
measure: Percentage of Participants With Best Overall Response [Clinical Benefit Rate (CBR)]
timeFrame: Baseline through study completion (up to 105.4 weeks)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Deaths
timeFrame: Baseline through study completion (up to 112.9 weeks)
measure: Serum Anti-IMC-A12 Antibody Assessment (Immunogenicity)
timeFrame: 30-day safety follow-up
Other outcomes:
Locations:
city: Aurora
country: United States
facility: ImClone Investigational Site
state: Colorado
city: Orlando
country: United States
facility: ImClone Investigational Site
state: Florida
city: Metairie
country: United States
facility: ImClone Investigational Site
state: Louisiana
city: Metairie
country: United States
facility: ImClone Investigational Site
state: Louisiana
city: Detroit
country: United States
facility: ImClone Investigational Site
state: Michigan
city: Saint Louis
country: United States
facility: ImClone Investigational Site
state: Missouri
city: Columbus
country: United States
facility: ImClone Investigational Site
state: Ohio
city: Brussels
country: Belgium
facility: ImClone Investigational Site
city: Leuven
country: Belgium
facility: ImClone Investigational Site
city: Wilrijk
country: Belgium
facility: ImClone Investigational Site
city: Bordeaux
country: France
facility: ImClone Investigational Site
city: Lyon
country: France
facility: ImClone Investigational Site
city: Paris
country: France
facility: ImClone Investigational Site
city: Toulouse
country: France
facility: ImClone Investigational Site
city: Dresden
country: Germany
facility: ImClone Investigational Site
city: Mannheim
country: Germany
facility: ImClone Investigational Site
city: Leiden
country: Netherlands
facility: ImClone Investigational Site
city: Warsaw
country: Poland
facility: ImClone Investigational Site
city: Barcelona
country: Spain
facility: ImClone Investigational Site
city: Barcelona
country: Spain
facility: ImClone Investigational Site
city: Barcelona
country: Spain
facility: ImClone Investigational Site
city: Barcelona
country: Spain
facility: ImClone Investigational Site
Study officials:
affiliation: Eli Lilly and Company
name: E-mail: ClinicalTrials@ ImClone.com
role: STUDY_DIRECTOR
References:
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.