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

Rhabdomyosarcoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00668148
• Other study ID #: 13925
• Secondary ID: 2007-006719-21CP
• Status: Completed
• Phase: Phase 2
• Start date: July 2008
• Est. completion date: February 2012

Study information

• Verified date: June 2018
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 113
• Est. completion date: February 2012
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adipocytic Sarcoma
• Ewing's Sarcoma /Peripheral Neuroectodermal Tumor (PNET)
• Leiomyosarcoma
• Neuroectodermal Tumors
• Neuroectodermal Tumors, Primitive
• Neuroectodermal Tumors, Primitive, Peripheral
• Rhabdomyosarcoma
• Sarcoma
• Sarcoma, Ewing
• Sarcoma, Synovial
• Synovial Sarcoma

Intervention

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.
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Belgium	ImClone Investigational Site	Brussels
Belgium	ImClone Investigational Site	Leuven
Belgium	ImClone Investigational Site	Wilrijk
France	ImClone Investigational Site	Bordeaux
France	ImClone Investigational Site	Lyon
France	ImClone Investigational Site	Paris
France	ImClone Investigational Site	Toulouse
Germany	ImClone Investigational Site	Dresden
Germany	ImClone Investigational Site	Mannheim
Netherlands	ImClone Investigational Site	Leiden
Poland	ImClone Investigational Site	Warsaw
Spain	ImClone Investigational Site	Barcelona
Spain	ImClone Investigational Site	Barcelona
Spain	ImClone Investigational Site	Barcelona
Spain	ImClone Investigational Site	Barcelona
United States	ImClone Investigational Site	Aurora	Colorado
United States	ImClone Investigational Site	Columbus	Ohio
United States	ImClone Investigational Site	Detroit	Michigan
United States	ImClone Investigational Site	Metairie	Louisiana
United States	ImClone Investigational Site	Metairie	Louisiana
United States	ImClone Investigational Site	Orlando	Florida
United States	ImClone Investigational Site	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Netherlands,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	Time to Response		Baseline to first evidence of confirmed CR or PR (up to 105.4 weeks)
Secondary	Duration of Response		Date of first response to the date of progression or death due to any cause (up to 105.4 weeks)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Serum Anti-IMC-A12 Antibody Assessment (Immunogenicity)		30-day safety follow-up