Relapsed resectable and unresectable Osteosarcoma, Ewing Sarcoma.
Conditions
Interventions
Product Name: anti-IGF-1R monoclonal antibody
Product Code: SCH 717454
Pharmaceutical Form: Concentrate for solution for infusion
CAS Number: 934235-44-6
Current Sponsor code: SCH 717454
Concentration
Sponsors
Schering Plough Research Institute
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. A subject must be 11 years of age or older and may be of any race, and gender (subjects between 4 and 10 years of age, inclusive, may be considered on a site-by-site basis) 2. A subject must have a diagnosis of histologically confirmed osteosarcoma or Ewing’s sarcoma; 3. A subject with either: a. relapsed and resectable osteosarcoma (to be included in Group 1) that: - has recurred after prior systemic treatment with active chemotherapy agents (ie, prior exposure to at least one chemotherapy regimen, ie, platinum and doxorubicin); and - must have had the confirmed relapse within 6 months of the immediate prior treatment of the osteosarcoma (longer intervals require discussion with the sponsor); and - must have a surgical or core biopsy tumor specimen (available to determine historical tumor proliferation), and the subject must not have been receiving tumor directed therapy at the time the specimen was obtained, or must have been progressing while on that treatment. The specimen should have been obtained within 8 months of study entry (specimens >8 months before study entry require discussion with the sponsor). b. relapsed and unresectable osteosarcoma (to be included in Group 2) that is refractory to standard therapy, ie has relapsed after prior systemic treatment with active chemotherapy agents (ie, prior exposure to a platinum and doxorubicin containing regimen). The subject must have measurable disease on a CT or MRI study performed during Screening (within 21 days of Day 1); c. Ewing’s sarcoma (to be included in Group 3) that is refractory to standard systemic therapy (ie, prior treatment with at least 3 of these agents: ifosfamide/etoposide; and cyclophosphamide, doxorubicin, and vincristine). The subject must have measurable disease on a CT or MRI study performed during Screening (within 21 days of Day 1). 4. A subject >16 years of age must have an Eastern Cooperative Oncology Group (ECOG) performance status of = 2; a subject = 16 years of age must have a Karnofsky performance status between 50% and 100% or a Lansky play scale between 50% and 100%; 5. A subject must have a minimum life expectancy of >8 weeks; 6. A subject must have adequate organ function within 3 weeks prior to Day 1 as evidenced by: a. hemoglobin =9 g/dL (=8 g/dL in subjects with Ewing’s sarcoma), b. absolute neutrophil count =1.5 x 10^9/L (=1.0 x 109/L in subjects with Ewing’s sarcoma), c. platelet count =100 x 109/L (=50 x 10^9/L in subjects with Ewing’s sarcoma), d. creatinine 8 months before study entry require discussion with the sponsor). b. relapsed and unresectable osteosarcoma (to be included in Group 2) that is refractory to standard therapy, ie has relapsed after prior systemic treatment with active chemotherapy agents (ie, prior exposure to a platinum and doxorubicin containing regimen). The subject must have measurable disease on a CT or MRI study performed during Screening (within 21 days of Day 1); c. Ewing’s sarcoma (to be included in Group 3) that is refractory to standard systemic therapy (ie, prior treatment with at least 3 of these agents: ifosfamide/etoposide; and cyclophosphamide, doxorubicin, and vincristine). The subject must have measurable disease on a CT or MRI study performed during Screening (within 21 days of Day 1). 4. A subject >16 years of age must have an Eastern Cooperative Oncology Group (ECOG) performance status of = 2; a subject = 16 years of age must have a Karnofsky performance status between 50% and 100% or a Lansky play scale between 50% and 100%; 5. A subject must have a minimum life expectancy of >8 weeks; 6. A subject must have adequate organ function within 3 weeks prior to Day 1 as evidenced by: a. hemoglobin =9 g/dL (=8 g/dL in subjects with Ewing’s sarcoma), b. absolute neutrophil count =1.5 x 10^9/L (=1.0 x 109/L in subjects with Ewing’s sarcoma), c. platelet count =100 x 109/L (=50 x 10^9/L in subjects with Ewing’s sarcoma), d. creatinine <1.5 x upper limit of normal (ULN) or creatinine clearance =60 mL/min, e. total bilirubin <1.5 x ULN, except for subjects with Gilbert’s disease, f. aspartate aminotransferase (AST)/serum glutamic-oxalacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) <3 x ULN, or in the presence of documented liver metastases =5 x ULN. Subjects with evidence of bone marrow involvement or single hematologic abnormalities (eg, ITP) may be permited on study on a case-by-case basis. Out-of-range laboratory values at Screening may be repeated once during the Screening Period. 7. A subject (and/or parent/guardian for subjects under the age of legal consent) must give written informed consent and be able to adhere to dose and visit schedules; 8. A female subject and a male subject’s female partner, of childbearing potential, must agree to use a medically accepted method of contraception prior to Screening, while receiving protocol-specified m
Exclusion criteria
Exclusion criteria: The subject will be excluded from entry if ANY of the criteria listed below are met: 1. A subject with a history of another malignancy (with the exception of nonmelanoma skin cancer or carcinoma in situ of the cervix treated with curative intent at least 2 years prior to start of treatment, or other adequately treated malignancy for which the subject has been disease free for =5 years); 2. A subject who has known treated or untreated leptomeningeal metastasis, or a metastatic central nervous system lesion; 3. A subject with a history of uncontrolled diabetes mellitus, defined as a hemoglobin A1C of =7.5% in a patient with known diabetes mellitus; 4 A subject with a recent myocardial infarction (within the past year); or a subject who at the time of Screening presents with unstable or uncontrolled angina, New York Heart Association (NYHA) Class III or IV congestive heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or clinically significant electrocardiogram (ECG) abnormality; 5. A subject with an active infection; 6. A subject with clinically significant hepatitis at Screening, or a subject that is hepatitis C antibody positive, hepatitis B surface antigen positive, or human immunodeficiency virus (HIV) seropositive; 7. A subject who has been treated with an anti-IGF-1R targeted drug or antibody; 8. A subject with known hypersensitivity to other antibodies, or any accompanying excipients associated with these medications; 9. A subject with persistent, unresolved common terminology criteria for adverse events (CTCAE) = Grade 2 drug-related toxicity associated with previous treatment except for alopecia (inclusion of subjects with persistent neuropathy or hearing loss =Grade 2 due to previous treatment require discussion with the sponsor); 10. A subject who has any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with the study evaluations or optimal participation in the study; 11. A subject who has received any treatment listed in Table 3 of Section 7.3.2 more recently than the indicated period prior to Screening or must continue to receive treatment that is listed in Table 3 of Section 7.3.2. Any other tumor-directed therapy must be discussed with the sponsor on a case-by-case basis; -Concurrent chemotherapy for the purpose of treating the tumor. wash out 21 days prior to Day 1. -Other monoclonal antibodies. wash out Four half lives of the monoclonal antibody prior to Day 1. -Immunosuppressive medication (eg, high-dose steroids). wash out Prior to Screening. -Investigational drugs wash out 21 days prior to Day 1. 12. A female subject who is breast-feeding, pregnant, intends to become pregnant, or has a positive pregnancy test at Screening; 13. A subject participating in any other clinical study with a potentially therapeutic agent or who has received another investigational product within 21 days prior to Day 1; 14. A subject unlikely to complete the study and appropriate follow-up visits. ;Exclusion criteria: The subject will be excluded from entry if ANY of the criteria listed below are met: 1. A subject with a history of another malignancy (with the exception of nonmelanoma skin cancer or carcinoma in situ of the cervix treated with curative intent at least 2 years prior to start of treatment, or other adequately treated malignancy for which the subject has been disease free for =5 years); 2. A subject who has known treated or untreated leptomeningeal metastasis, or a metastatic central nervous system lesion; 3. A subject with a history of uncontrolled diabetes mellitus, defined as a hemoglobin A1C of =7.5% in a patient with known diabetes mellitus; 4 A subject with a recent myocardial infarction (within the past year); or a subject who at the time of Screening presents with unstable or uncontrolled angina, New York Heart Association (NYHA) Class III or IV congestive heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or clinically significant electrocardiogram (ECG) abnormality; 5. A subject with an active infection; 6. A subject with clinically significant hepatitis at Screening, or a subject that is hepatitis C antibody positive, hepatitis B surface antigen positive, or human immunodeficiency virus (HIV) seropositive; 7. A subject who has been treated with an anti-IGF-1R targeted drug or antibody; 8. A subject with known hypersensitivity to other antibodies, or any accompanying excipients associated with these medications; 9. A subject with persistent, unresolved common terminology criteria for adverse events (CTCAE) = Grade 2 drug-related toxicity associated with previous treatment except for alopecia (inclusion of subjects with persistent neuropathy or hearing loss =Grade 2 due to previous treatment require discussion with the sponsor); 10. A subject who has any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with the study evaluations or optimal participation in the study; 11. A subject who has received any treatment listed in Table 3 of Section 7.3.2 more recently than the indicated period prior to Screening or must continue to receive treatment that is listed in Table 3 of Section 7.3.2. Any other tumor-directed therapy must be discussed with the sponsor on a case-by-case basis; -Concurrent chemotherapy for the purpose of treating the tumor. wash out 21 days prior to Day 1. -Other monoclonal antibodies. wash out Four half lives of the monoclonal antibody prior to Day 1. -Immunosuppressive medication (eg, high-dose steroids). wash out Prior to Screening. -Investigational drugs wash out 21 days prior to Day 1. 12. A female subject who is breast-feeding, pregnant, intends to become pregnant, or has a positive pregnancy test at Screening; 13. A subject participating in any other clinical study with a potentially therapeutic agent or who has received another investigational product within 21 days prior to Day 1; 14. A subject unlikely to complete the study and appropriate follow-up visits.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objectives: Group 1 -To determine tumor cell proliferation response after dosing with SCH 717454 in Subjects with resectable osteosarcoma that has relapsed after standard systemic therapy compared to the subject’s historical tumor cell proliferation. Group 2 -To determine the World Health Organization (WHO) and Response Evaluation Criteria in Solid Tumors (RECIST)-defined radiological response rate to SCH 717454 in subjects with unresectable osteosarcoma refractory to standard therapy. Response rate for Group 2 is defined as the proportion of subjects who achieve a complete response (CR), a partial response (PR), or stable disease (SD) for (symbol for greater than or equal to) 6 months. Group 3 -To determine the WHO and RECIST-defined radiological response rate to SCH 717454 in subjects with Ewing’s sarcoma refractory to standard therapy. Response rate for Group 3 is defined as the proportion of subjects who achieve a CR or a PR. ;Secondary Objective: Group 1: Determine time to relapse after dosing w/SCH 717454 in subjects w/resectable osteosarcoma that has relapsed after standard systemic therapy. Group 2/3: Determine duration of response & time to progression after dosing w/SCH 717454 in subjects w/either unresectable osteosarcome or refractory Ewing's sarcoma. All Groups: Assess the overall survival of each group, evaluate safety & tolerability of SCH 717454 administered every 2 weeks in subjects w/osteosarcoma & Ewing’s sarcoma who have relapsed after standard systemic therapy, evaluate peripheral blood levels of: -Insulin-like Growth Factor I (IGF-I), & IGF-II -Insulin-like Growth Factor binding protein 2 (IGFBP-2), & Insulin-like Growth Factor binding protein 3 (IGFBP-3) -Insulin-like Growth Factor 1 Receptor (IGF-1R) expression on peripheral blood mononuclear cells (PBMC) by fluorescence activated cell sorting (FACS), To determine the incidence of anti-SCH 717454 antibodies To evaluate serum SCH 717454 concentrations ;Primary end poi | — |
Countries
Czech Republic, France, Germany, Hungary, Italy, Netherlands, Norway, Portugal, Spain, Sweden, United Kingdom
Contacts
Public Contact; ;
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Outcome results
None listed