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A Five-Tier, Phase 2 Open-Label Study of IMC-A12 Administered as a Single Agent
This study is currently recruiting participants.
Verified by ImClone LLC, November 2009
First Received: April 25, 2008   Last Updated: November 6, 2009   History of Changes
Sponsor: ImClone LLC
Information provided by: ImClone LLC
ClinicalTrials.gov Identifier: NCT00668148
  Purpose

This multicenter, open-label, phase 2 study will enroll approximately 185 patients with metastatic or advanced sarcoma, to assess the efficacy and tolerability of IMC-A12 monotherapy for this indication. The patient population will be stratified into five tiers according to diagnosis:

  1. Ewing's sarcoma/PNET
  2. rhabdomyosarcoma
  3. leiomyosarcoma
  4. adipocytic sarcoma
  5. synovial sarcoma.

A total of 85 patients will be enrolled initially, 17 in each tier. Patients will receive single agent IMC-A12 as a 10 mg/kg intravenous (I.V.) infusion over 1 hour every 2 weeks. A treatment cycle will be defined as 6 weeks, with radiological evaluation every cycle.

The Simon two-stage design will be applied separately to each tier; safety and response in the initial 17 patients in each tier will be used to determine whether to extend enrollment to the target total of 37 patients per tier (for a total of 185 subjects)


Condition Intervention Phase
Ewing's Sarcoma /Peripheral Neuroectodermal Tumor (PNET)
Rhabdomyosarcoma
Leiomyosarcoma
Adipocytic Sarcoma
Synovial Sarcoma
Biological: IMC-A12
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study
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

Resource links provided by NLM:


Further study details as provided by ImClone LLC:

Primary Outcome Measures:
  • To determine the progression-free survival rate assessed 12 wks after the initiation of IMC-A12 monotherapy, administered every 2 weeks to pts w/previously-treated, advanced or metastatic soft tissue and Ewing's sarcoma/PNET. [ Time Frame: 12 weeks after the initiation of IMC-A12 monotherapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the overall PFS rate [ Time Frame: 12 weeks after the initiation of IMC-A12 monotherapy ] [ Designated as safety issue: No ]
  • To evaluate the objective response rate (ORR) [ Time Frame: 12 weeks after the initiation of IMC-A12 monotherapy ] [ Designated as safety issue: No ]
  • To determine the time to onset of response and the duration of response [ Time Frame: 12 weeks after the initiation of IMC-A12 monotherapy ] [ Designated as safety issue: No ]
  • To determine overall survival (OS) [ Time Frame: 12 weeks after the initiation of IMC-A12 monotherapy ] [ Designated as safety issue: No ]
  • To determine the clinical benefit rate (CBR) [ Time Frame: 12 weeks after the initiation of IMC-A12 monotherapy ] [ Designated as safety issue: No ]
  • To evaluate the safety, tolerability, and adverse event profile of IMC-A12 in this context [ Time Frame: 12 weeks after the initiation of IMC-A12 monotherapy ] [ Designated as safety issue: Yes ]
  • To assess the development of antibodies against IMC-A12 [ Time Frame: 12 weeks after the initiation of IMC-A12 monotherapy ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 185
Study Start Date: April 2008
Estimated Study Completion Date: August 2010
Estimated Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
IMC-A12: Experimental
IMC-A12 injection for intravenous use, supplied in single-use 90 mg/20-mL or 250 mg/50-mL vials containing 4.5 mg/mL in phosphate-buffered saline or 5 mg/mL in citrate-based saline, respectively, and administered intravenously at a dose of 10 mg/kg every 2 weeks.
Biological: IMC-A12

IMC-A12 injection for intravenous use, supplied in single-use 90 mg/20-mL or 250 mg/50-mL vials containing 4.5 mg/mL in phosphate-buffered saline or 5 mg/mL in citrate-based saline, respectively, and administered intravenously at a dose of 10 mg/kg every 2 weeks. A treatment cycle will be defined as 6 weeks, with radiological evaluation every cycle.

There will be no interruption between treatment cycles. Patients will be treated until there is evidence of disease progression, toxicity requiring cessation, or withdrawal of consent.


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 patients with previously-treated, advanced or metastatic soft tissue and Ewing's sarcoma/PNET.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion:

  1. The patient has 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.
  2. The patient has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded), with minimum lesion size ≥ 2 cm on conventional measurement techniques or ≥ 1 cm on spiral computed tomography (CT) scan.
  3. The patient has at least one measurable lesion located outside of a previously irradiated area.
  4. The patient has radiographic documentation of disease progression within 6 months prior to study entry (see Section 11.4 for a full definition of disease progression).
  5. The patient has relapsed, refractory, and/or metastatic disease, incurable by surgery, radiotherapy, or other conventional systemic therapy.
  6. The patient must have either been considered ineligible for systemic chemotherapy or received at least one previous regimen for relapsed, refractory, and/or metastatic disease.
  7. The patient is age ≥ 12 years.
  8. The patient has a life expectancy of > 3 months.
  9. The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1.
  10. The patient has adequate hematologic function as defined by absolute neutrophil count ≥ 1500/μL, hemoglobin ≥ 9 g/dL, and platelet count ≥ 100,000/μL.
  11. The patient has adequate hepatic function as defined by a total bilirubin ≤ 1.5 x the upper limit of normal (ULN), and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x the ULN (or ≤ 5 x the ULN in the presence of known liver metastases).
  12. The patient has adequate coagulation function as defined by international normalized ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) no more than 5 seconds above the ULN.
  13. The patient has adequate renal function as defined by serum creatinine ≤ 1.5 x the institutional ULN or creatinine clearance ≥ 60 mL/min for patients with creatinine levels above 1.5 x the ULN.
  14. The patient has fasting serum glucose < 120 mg/dL or below the ULN.
  15. Because the teratogenicity of IMC-A12 is not known, 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.
  16. The patient or his or her legal guardian has the ability to understand and the willingness to sign a written informed consent document

Exclusion

  1. The patient has uncontrolled brain or leptomeningeal metastases.
  2. The patient has not recovered to grade ≤ 1 from adverse events due to agents administered more than 3 weeks prior to study entry.
  3. The patient is receiving any other investigational agent(s).
  4. The patient has undergone major surgery, hormonal therapy (other than replacement), chemotherapy, radiotherapy, or any form of investigational therapy within 3 weeks prior to enrollment.
  5. The patient has a history of treatment with other agents targeting the IGFR.
  6. The patient has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to that of IMC-A12.
  7. The patient has poorly controlled diabetes mellitus. Patients with a history of diabetes mellitus are allowed to participate, provided that their blood glucose is within normal range (fasting < 120 mg/dL or below ULN) and that they are on a stable dietary or therapeutic regimen for this condition.
  8. The patient has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, uncontrolled hypertension, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  9. The patient is receiving therapy with immunosuppressive agents.
  10. The patient is pregnant or breastfeeding.
  11. The patient is known to be positive for infection with the human immunodeficiency virus.
  12. The patient has a history of another primary cancer, with the exception of: a)curatively resected non-melanomatous skin cancer; b) curatively treated cervical carcinoma in-situ; or c) other primary solid tumor curatively resected treated with no known active disease present and no treatment administered for the last 3 years.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00668148

Contacts
Contact: Paul Windt 908-541-8151 paul.windt@imclone.com

Locations
United States, Colorado
University of Colorado Health Sciences Center Recruiting
Aurora, Colorado, United States, 80045
Contact: Tiffany Colvin     720-848-0664     tiffany.colvin@uchsc.edu    
Principal Investigator: Anthony Elias, MD            
The Children's Hospital Recruiting
Aurora, Colorado, United States, 80045
Contact: Deb Schissel         DSchissel@tchden.org    
Principal Investigator: Lia Gore, MD            
United States, Florida
MD Anderson Cancer Center Orlando Recruiting
Orlando, Florida, United States, 32806
Contact: Meg Caldwell     321-841-6653     meghan.cadwell@orlandohealth.com    
Principal Investigator: Gregory K Pennock, MD            
United States, Louisiana
Jayne Gurtler MD Recruiting
Metairie, Louisiana, United States, 70006-2921
Contact: Jeannette Vicknair     504-885-0577     jvicknair@metaireoncologists.org    
Principal Investigator: Jayne Gurtler, MD            
United States, Michigan
Wayne State University Recruiting
Detroit, Michigan, United States, 48201-2014
Contact: Radika Yalamanchili     313-576-9364        
Principal Investigator: Shirish Gadgeel, MD            
United States, Missouri
Washington University School of Medicine Recruiting
St Louis, Missouri, United States, 63110
Contact: Kristina Williams     314-362-6963     kjwillia1@im.wustl.edu    
Principal Investigator: Douglas Adkins, MD            
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Dina Aziz     614-293-7961        
Principal Investigator: Anterpreet Neki, MD            
Belgium
Institute Jules Bordet Recruiting
Brussels, Belgium, 1000
Contact: Adeline Boissy     32 541 7245     adeline.boissy@bordet.be    
Principal Investigator: Thierry Gil, Dr            
U.Z. Gasthuisberg, Leuven Recruiting
Leuven, Belgium, 3000
Contact: Inge Le Beer     32 1634 1020     inge.le.beer@uz.kuleuven.ac.be    
Principal Investigator: Patrick Schoffski, Dr            
AS St. Augustinus Recruiting
Wilrijk, Belgium, 2610
Contact: Hilde Maes     32 443 3759     hilde.maes@gza.be    
Principal Investigator: Luc Yves Dirix, Dr            
France
Centre Leon Berard Recruiting
Lyon, France, 69008
Contact: Jean-Yves Blay, Prof.     33-4797-927-57     blay@lyon.fnclcc.fr    
Principal Investigator: Jean-Yves Blay, Prof.            
Netherlands
Leids Universitair Medisch Centrum Recruiting
Leiden, Netherlands, 2333
Contact: Inge Roozen     31-71-526-1987        
Principal Investigator: Hans Gelderblom, Dr            
Poland
Centrum Onkologii Instytut im Marii Sklodowskiej-Curie Recruiting
Warsaw, Poland
Contact: Piotr Rutkowski, Dr     48-501-153-384        
Principal Investigator: Wlodzimierz Ruka, Prof            
Spain
Hospital Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Contact: Mireia Centelles     34-93-489-4375        
Principal Investigator: Maria V Morales, Dr            
Institut Català d'Oncologia (ICO)-L'Hospitalet Recruiting
Barcelona, Spain, 08907
Contact: Pepi Rivera     34-93-260-7332        
Principal Investigator: Xavier G del Muro, Dr            
Hospital De Sant Pau Recruiting
Barcelona, Spain, 08025
Contact: Rosa Sánchez     34-93-553-7116        
Principal Investigator: Antonio Lopez-Pousa, Dr            
Sponsors and Collaborators
ImClone LLC
Investigators
Study Director: Eric Rowinsky, MD ImClone LLC
  More Information

No publications provided

Responsible Party: ImClone LLC ( Eric Rowinsky/ Chief Medical Officer )
Study ID Numbers: CP13-0707, EudraCT Number: 2007-006719-21
Study First Received: April 25, 2008
Last Updated: November 6, 2009
ClinicalTrials.gov Identifier: NCT00668148     History of Changes
Health Authority: United States: Food and Drug Administration;   Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products;   Netherlands: The Central Committee on Research Involving Human Subjects (CCMO);   Spain: Agencia Espanola de Medicamentos y Productos Sanitarios;   Germany: PAUL-EHRLICH-INSTITUT (BUNDESAMT FUER SERA UND IMPFSTOFFE);   Belgium: Madame Greet Musch, Responsable departement R&D;   France: Agence Francaise de Securite des Produits de Sante (AFSSAPS)

Keywords provided by ImClone LLC:
Sarcoma
Ewing's sarcoma / peripheral neuroectodermal tumor (PNET);
rhabdomyosarcoma;
leiomyosarcoma;
adipocytic sarcoma
synovial sarcoma

Additional relevant MeSH terms:
Neoplasms, Muscle Tissue
Neuroectodermal Tumors, Primitive
Neoplasms by Histologic Type
Leiomyosarcoma
Myosarcoma
Neoplasms, Nerve Tissue
Osteosarcoma
Sarcoma, Synovial
Neuroectodermal Tumors
Neoplasms, Connective and Soft Tissue
Sarcoma, Ewing's
Neoplasms
Neoplasms, Bone Tissue
Neoplasms, Germ Cell and Embryonal
Sarcoma
Neoplasms, Connective Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Glandular and Epithelial
Rhabdomyosarcoma

ClinicalTrials.gov processed this record on November 25, 2009