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

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00668148
• Collaborator: (none)
• Enrollment: 113
• Locations: 22
• Arm: 1
• Duration (Months): 43
• Patients Per Site: 5.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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); Biological: IMC-A12 (cixutumumab); Biological: IMC-A12 (cixutumumab); Biological: IMC-A12 (cixutumumab); 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 Design

• Study Type: Interventional
• Actual Enrollment: 113 participants
• Allocation: N/A
• 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: Jul 1, 2008
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Progression-Free Survival (PFS) at 12 Weeks [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) [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)] [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 [Baseline to first evidence of confirmed CR or PR (up to 105.4 weeks)]

4. Duration of Response [Date of first response to the date of progression or death due to any cause (up to 105.4 weeks)]

5. Overall Survival (OS) [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)] [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 [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) [30-day safety follow-up]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ImClone Investigational Site	Aurora	Colorado	United States	80045
2	ImClone Investigational Site	Orlando	Florida	United States	32806
3	ImClone Investigational Site	Metairie	Louisiana	United States	70006-2921
4	ImClone Investigational Site	Metairie	Louisiana	United States	70006
5	ImClone Investigational Site	Detroit	Michigan	United States	48201-2014
6	ImClone Investigational Site	Saint Louis	Missouri	United States	63110
7	ImClone Investigational Site	Columbus	Ohio	United States	43210
8	ImClone Investigational Site	Brussels		Belgium	1000
9	ImClone Investigational Site	Leuven		Belgium	3000
10	ImClone Investigational Site	Wilrijk		Belgium	2610
11	ImClone Investigational Site	Bordeaux		France	33076
12	ImClone Investigational Site	Lyon		France	69008
13	ImClone Investigational Site	Paris		France	75231
14	ImClone Investigational Site	Toulouse		France	31052
15	ImClone Investigational Site	Dresden		Germany	01307
16	ImClone Investigational Site	Mannheim		Germany	68167
17	ImClone Investigational Site	Leiden		Netherlands	2333 ZA
18	ImClone Investigational Site	Warsaw		Poland	02-781
19	ImClone Investigational Site	Barcelona		Spain	08025
20	ImClone Investigational Site	Barcelona		Spain	08035
21	ImClone Investigational Site	Barcelona		Spain	08041
22	ImClone Investigational Site	Barcelona		Spain	08907

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00668148
• Other Study ID Numbers: 13925; 2007-006719-21; CP13-0707; I5A-IE-JAEC
• First Posted: Apr 29, 2008
• Last Update Posted: Jul 17, 2018
• Last Verified: Jun 1, 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; Rhabdomyosarcoma; Sarcoma, Ewing; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Leiomyosarcoma; Sarcoma, Synovial; Neuroectodermal Tumors, Primitive, Peripheral; Antibodies, Monoclonal

Study Results

Participant Flow

Pre-assignment Detail	Presented are the reasons the participants discontinued from study treatment.

Arm/Group Title	Entire Study Population
Arm/Group Description	IMC-A12 (cixutumumab) 10 milligrams per kilogram (mg/kg) dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Participants were stratified into 5 arms according to the disease condition: Ewing's Sarcoma/peripheral neuroectodermal tumor (PNET), rhabdomyosarcoma, leiomyosarcoma, adipocytic sarcoma, and synovial sarcoma. Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawal of consent.
Period Title: Overall Study
STARTED	113
Received at Least 1 Dose of Study Drug	111
COMPLETED	103
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	Entire Study Population
Arm/Group Description	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Participants were stratified into 5 arms according to the disease condition: Ewing's Sarcoma/PNET, rhabdomyosarcoma, leiomyosarcoma, adipocytic sarcoma, and synovial sarcoma. Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawal of consent.
Overall Participants	111
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	47.0 (10.3)
Sex: Female, Male (Count of Participants)
Female	54 48.6%
Male	57 51.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 7.2%
Not Hispanic or Latino	102 91.9%
Unknown or Not Reported	1 0.9%
Race/Ethnicity, Customized (Count of Participants)
White	101 91%
Black	5 4.5%
Other	5 4.5%
Region of Enrollment (Count of Participants)
France	15 13.5%
United States	50 45%
Poland	7 6.3%
Spain	9 8.1%
Belgium	23 20.7%
Germany	1 0.9%
Netherlands	6 5.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Progression-Free Survival (PFS) at 12 Weeks
Description	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.
Time Frame	Baseline to Disease Progression or Death Due to Any Cause Up To 12 Weeks

Outcome Measure Data

Analysis Population Description

Enrolled participants who received any quantity of IMC-A12.

Arm/Group Title	Ewing's Sarcoma/PNET	Rhabdomyosarcoma	Leiomyosarcoma	Adipocytic Sarcoma	Synovial Sarcoma	Total
Arm/Group Description	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawal of consent.	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawal of consent.	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawal of consent.	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawal of consent.	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawal of consent.	Total of all reporting groups.
Measure Participants	18	17	22	37	17	111
Number (95% Confidence Interval) [percentage of participants]	27.3 24.6%	12.5 NaN	25.4 NaN	50.0 NaN	21.4 NaN	31.9 NaN

2. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	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.
Time Frame	Baseline to measured PD (up to 105.4 weeks)

Outcome Measure Data

Analysis Population Description

Enrolled participants who received any quantity of IMC-A12. Three (3) participants in Ewing's sarcoma/PNET, 1 participant in rhabdomyosarcoma, 4 participants in leiomyosarcoma, 6 participants in adipocytic sarcoma, and 3 participants in synovial sarcoma groups were censored for analysis.

Arm/Group Title	Ewing's Sarcoma/PNET	Rhabdomyosarcoma	Leiomyosarcoma	Adipocytic Sarcoma	Synovial Sarcoma	Total
Arm/Group Description	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawn consent.	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawn consent.	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawn consent.	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawn consent.	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawn consent.	Total of all reporting groups.
Measure Participants	18	17	22	37	17	111
Median (95% Confidence Interval) [weeks]	6.4	6.1	6.0	12.1	6.4	6.7

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Enrolled participants who received any quantity of IMC-A12.

Arm/Group Title	Ewing's Sarcoma/PNET	Rhabdomyosarcoma	Leiomyosarcoma	Adipocytic Sarcoma	Synovial Sarcoma	Total
Arm/Group Description	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawn consent.	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawn consent.	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawn consent.	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawn consent.	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawn consent.	Total of all reporting groups.
Measure Participants	18	17	22	37	17	111
Number (95% Confidence Interval) [percentage of participants]	5.6 5%	0 NaN	0 NaN	2.7 NaN	0 NaN	1.8 NaN

4. Secondary Outcome

Title	Time to Response
Time Frame	Baseline to first evidence of confirmed CR or PR (up to 105.4 weeks)

Outcome Measure Data

Analysis Population Description

Zero participants analyzed. Time to Response for CR and PR data was not collected for analysis per study report.

Arm/Group Title	Entire Study Population
Arm/Group Description	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Participants were stratified into 5 arms according to the disease condition: Ewing's Sarcoma/PNET, rhabdomyosarcoma, leiomyosarcoma, adipocytic sarcoma, and synovial sarcoma. Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawal of consent.
Measure Participants	0

5. Secondary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

Zero participants analyzed. Duration to Response for CR and PR data was not collected for analysis per study report.

Arm/Group Title	Entire Study Population
Arm/Group Description	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Participants were stratified into 5 arms according to the disease condition: Ewing's Sarcoma/PNET, rhabdomyosarcoma, leiomyosarcoma, adipocytic sarcoma, and synovial sarcoma. Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawal of consent.
Measure Participants	0

6. Secondary Outcome

Title	Overall Survival (OS)
Description	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.
Time Frame	Baseline to date of death from any cause (up to 112.9 weeks)

Outcome Measure Data

Analysis Population Description

Enrolled participants who received any quantity of IMC-A12. Five (5) participants in Ewing's sarcoma/PNET, 4 participants in rhabdomyosarcoma, 12 participants in leiomyosarcoma, 11 participants in adipocytic sarcoma, and 5 participants in synovial sarcoma groups were censored for analysis.

Arm/Group Title	Ewing's Sarcoma/PNET	Rhabdomyosarcoma	Leiomyosarcoma	Adipocytic Sarcoma	Synovial Sarcoma	Total
Arm/Group Description	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawal of consent.	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawal of consent.	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawal of consent.	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawal of consent.	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawal of consent.	Total of all reporting groups.
Measure Participants	18	17	22	37	17	111
Median (95% Confidence Interval) [weeks]	24.1	23.6	NA	46.4	56.3	38.4

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Enrolled participants who received any quantity of IMC-A12.

Arm/Group Title	Ewing's Sarcoma/PNET	Rhabdomyosarcoma	Leiomyosarcoma	Adipocytic Sarcoma	Synovial Sarcoma	Total
Arm/Group Description	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawal of consent.	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawal of consent.	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawal of consent.	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawal of consent.	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawal of consent.	Total of all reporting groups.
Measure Participants	18	17	22	37	17	111
Number (95% Confidence Interval) [percentage of participants]	33.3 30%	23.5 NaN	40.9 NaN	56.8 NaN	35.3 NaN	41.4 NaN

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Enrolled participants who received any quantity of IMC-A12.

Arm/Group Title	Entire Study Population
Arm/Group Description	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Participants were stratified into 5 arms according to the disease condition: Ewing's Sarcoma/PNET, rhabdomyosarcoma, leiomyosarcoma, adipocytic sarcoma, and synovial sarcoma. Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawal of consent.
Measure Participants	111
Any TEAE	108 97.3%
Serious TEAE	56 50.5%
Deaths Due to Disease Progression	10 9%
Death Due to Other Cause	1 0.9%
Death Due to AE	1 0.9%

9. Secondary Outcome

Title	Serum Anti-IMC-A12 Antibody Assessment (Immunogenicity)
Time Frame	30-day safety follow-up

Outcome Measure Data

Analysis Population Description

Zero participants analyzed. Analysis was not performed due to lack of available assay.

Arm/Group Title	Entire Study Population
Arm/Group Description	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Participants were stratified into 5 arms according to the disease condition: Ewing's Sarcoma/PNET, rhabdomyosarcoma, leiomyosarcoma, adipocytic sarcoma, and synovial sarcoma. Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawal of consent.
Measure Participants	0

Adverse Events

Arm/Group Title	Entire Study Population
Arm/Group Description	IMC-A12 (cixutumumab) 10 mg/kg dose administered as intravenous infusion over a period of 1 hour once every 2 weeks (6-week cycle). Participants were stratified into 5 arms according to the disease condition: Ewing's sarcoma/PNET, rhabdomyosarcoma, leiomyosarcoma, adipocytic sarcoma, and synovial sarcoma. Treatment was continued until there was evidence of disease progression, unacceptable toxicity, or withdrawal of consent.
All Cause Mortality
	Entire Study Population
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Entire Study Population
	Affected / at Risk (%)	# Events
Total	56/111 (50.5%)
Blood and lymphatic system disorders
Anaemia	2/111 (1.8%)	3
Neutropenia	1/111 (0.9%)	1
Thrombocytopenia	1/111 (0.9%)	1
Cardiac disorders
Cardiac arrest	1/111 (0.9%)	2
Eye disorders
Chorioretinopathy	1/111 (0.9%)	1
Gastrointestinal disorders
Haematemesis	1/111 (0.9%)	1
Malabsorption	1/111 (0.9%)	1
Nausea	1/111 (0.9%)	1
Retroperitoneal haemorrhage	1/111 (0.9%)	1
Subileus	1/111 (0.9%)	1
Vomiting	1/111 (0.9%)	1
General disorders
Asthenia	1/111 (0.9%)	1
Chest pain	1/111 (0.9%)	1
Disease progression	14/111 (12.6%)	16
General physical health deterioration	2/111 (1.8%)	2
Infusion related reaction	1/111 (0.9%)	1
Mucosal inflammation	1/111 (0.9%)	1
Non-cardiac chest pain	1/111 (0.9%)	1
Pain	6/111 (5.4%)	7
Infections and infestations
Catheter related infection	1/111 (0.9%)	1
Cellulitis	1/111 (0.9%)	1
Endocarditis bacterial	1/111 (0.9%)	1
Infection	1/111 (0.9%)	1
Pneumonia	3/111 (2.7%)	3
Pyelonephritis	1/111 (0.9%)	1
Tracheobronchitis	1/111 (0.9%)	1
Urinary tract infection	1/111 (0.9%)	1
Injury, poisoning and procedural complications
Post procedural haemorrhage	1/111 (0.9%)	1
Spinal compression fracture	2/111 (1.8%)	2
Metabolism and nutrition disorders
Hyperglycaemia	2/111 (1.8%)	4
Hypocalcaemia	1/111 (0.9%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	1/111 (0.9%)	1
Back pain	1/111 (0.9%)	1
Pain in extremity	1/111 (0.9%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion	1/111 (0.9%)	1
Neoplasm progression	1/111 (0.9%)	1
Tumour haemorrhage	1/111 (0.9%)	1
Tumour pain	3/111 (2.7%)	4
Nervous system disorders
Peripheral sensory neuropathy	1/111 (0.9%)	1
Spinal cord compression	1/111 (0.9%)	1
Syncope	1/111 (0.9%)	1
Psychiatric disorders
Anxiety	1/111 (0.9%)	1
Renal and urinary disorders
Renal failure	1/111 (0.9%)	1
Renal failure acute	3/111 (2.7%)	3
Reproductive system and breast disorders
Vaginal haemorrhage	1/54 (1.9%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	4/111 (3.6%)	4
Haemoptysis	4/111 (3.6%)	5
Hypoxia	1/111 (0.9%)	1
Pleural effusion	1/111 (0.9%)	1
Pneumothorax	2/111 (1.8%)	2
Pulmonary embolism	1/111 (0.9%)	1
Respiratory failure	1/111 (0.9%)	1
Vascular disorders
Deep vein thrombosis	1/111 (0.9%)	1
Haemorrhage	1/111 (0.9%)	1
Phlebitis	1/111 (0.9%)	1
Other (Not Including Serious) Adverse Events
	Entire Study Population
	Affected / at Risk (%)	# Events
Total	97/111 (87.4%)
Blood and lymphatic system disorders
Anaemia	13/111 (11.7%)	29
Thrombocytopenia	6/111 (5.4%)	10
Gastrointestinal disorders
Abdominal pain	10/111 (9%)	24
Constipation	16/111 (14.4%)	18
Diarrhoea	25/111 (22.5%)	42
Nausea	28/111 (25.2%)	32
Vomiting	15/111 (13.5%)	18
General disorders
Asthenia	17/111 (15.3%)	81
Chest pain	6/111 (5.4%)	6
Fatigue	26/111 (23.4%)	36
Mucosal inflammation	6/111 (5.4%)	7
Oedema peripheral	7/111 (6.3%)	8
Investigations
Activated partial thromboplastin time prolonged	6/111 (5.4%)	7
Alanine aminotransferase increased	6/111 (5.4%)	8
Blood creatinine increased	13/111 (11.7%)	22
Haemoglobin decreased	6/111 (5.4%)	19
Weight decreased	11/111 (9.9%)	14
Metabolism and nutrition disorders
Anorexia	19/111 (17.1%)	22
Hyperglycaemia	22/111 (19.8%)	60
Hyponatraemia	8/111 (7.2%)	9
Musculoskeletal and connective tissue disorders
Arthralgia	12/111 (10.8%)	13
Back pain	9/111 (8.1%)	10
Muscle spasms	13/111 (11.7%)	20
Musculoskeletal pain	7/111 (6.3%)	8
Pain in extremity	6/111 (5.4%)	8
Nervous system disorders
Dizziness	6/111 (5.4%)	7
Headache	12/111 (10.8%)	17
Respiratory, thoracic and mediastinal disorders
Cough	14/111 (12.6%)	15
Dyspnoea	12/111 (10.8%)	14
Skin and subcutaneous tissue disorders
Alopecia	6/111 (5.4%)	6
Rash	8/111 (7.2%)	8

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.