E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ewing’s sarcoma and other sarcoma subtypes |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10015560 |
E.1.2 | Term | Ewing's sarcoma |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To determine the overall objective response rate of R1507 in patients with recurrent or refractory osteosarcoma, synovial sarcoma, rhabdomyosarcoma and other sarcomas of the following subtypes: alveolar soft part sarcoma, desmoplastic small round cell tumor, extraskeletal myxoid chondrosarcoma, clear cell sarcoma, and myxoid liposarcoma. 2. To determine the progression-free survival at 18 weeks from start of treatment of patients with progressive, recurrent or refractory Ewing’s sarcoma (Ewing’s family of tumors) treated with R1507. |
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E.2.2 | Secondary objectives of the trial |
1. To estimate the duration of response, progression-free survival rate at 18 weeks from start of treatment and overall progression-free survival of patients with recurrent or refractory sarcomas of the following subtypes who were treated with R1507. 2. To determine the overall objective response rate, response duration, overall progression-free survival and overall survival of patients with progressive, recurrent or refractory Ewing’s sarcoma (Ewing’s family of tumors) treated with R1507. 3. To define the population pharmacokinetic profile of R1507 in selected study patients. 4. To define the tolerability and adverse event profile of R1507 in sarcoma patients. Exploratory Objective: 1. To explore changes in PET scans in patients treated with R1507. 2. To explore serum biomarkers and their potential correlations with pharmacokinetics and clinical response
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Patients must have histologically or cytologically confirmed: Ewing’s sarcoma (Ewing’s family of tumors, ESFT); Osteosarcoma ; Synovial sarcoma ; Rhabdomyosarcoma ; Other sarcomas of the following subtypes (Alveolar soft part sarcoma ,Desmoplastic small round cell tumors, Extraskeletal myxoid chondrosarcoma , Clear cell sarcoma ,Myxoid Liposarcoma ). 2) Patients must have had histological verification of malignancy by central pathology review (to be completed within 6 weeks of study entry). 3) All patients must have recurrent or refractory tumors with no known curative treatment options according to the judgment of the investigator. For the Ewing’s and ESFT subtype the disease must be progressive. 4) Age > or =12 years. 5) Life expectancy of at least 6 weeks. 6) Karnofsky performance status of > or =70% 7) Patients must have measurable disease defined as lesions that can be measured in 2 dimensions by medical imaging techniques such as CT or MRI. Ascites, pleural fluid, bone marrow disease and lesions seen on PET scan only are not considered measurable. 8) Adequate organ function 8.1 Bone marrow (in the absence of bone marrow involvement by neoplasia) 8.1.1 Absolute neutrophil count > or = 1.5 x 10exp9/L (being > or = 30 days off growth factors 8.1.2 Platelet count > or = 75,000/mL *in patients with documented bone marrow involvement by neoplasia, no minimum ANC or platelet count is necessary at the discretion of the investigator 8.2 Hepatic 8.2.1 Total bilirubin < or = 1.5 times the upper limit of normal for age 8.2.2 ALT /AST (SGPT/SGOT) < or = 3x the ULN for the reference lab (< or = 5 x the ULN for the reference lab in the presence of known hepatic metastasis, adjusted for age) 8.3 Renal 8.3.1 Creatinine clearance > or =70 ml/min/1.73mexp2 or 8.3.2 Serum creatinine < 1.5 x ULN per age. 9) Prior Therapy 9.1 Time elapsed from previous therapy must be > or = 3 weeks. Patients must be recovered from the effects of any prior surgery, radiotherapy or systemic therapy, including any investigational therapy. 9.2 Patients who have undergone autologous hematopoietic stem cell transplantation (HSCT) will be eligible once they have recovered from all toxicities from therapy (< or = grade 1 except for alopecia). Patients who have received allogeneic HSCT will be eligible 6 months after the procedure provided there is no evidence of active graft-versus-host disease and immunosuppressive treatment has been discontinued for at least 30 days. 9.3 Patients with central nervous system (CNS) disease are eligible for enrollment if they have received prior radiotherapy or surgery to sites of CNS metastatic disease, have been off glucocorticoids for at least 4 weeks, have no overt evidence of neurological deficit and are > or = 6 weeks from completion of brain irradiation. 10) Patients or their legal representative must be able to read, understand and provide written informed consent to participate in the trial. Patients younger than 18 years of age should provide assent to participate in the trial. 11) Females of childbearing potential as well as fertile males and their partners must agree to use an effective form of contraception during the study and for 120 days following the last dose of study medication. An effective form of contraception is use of an oral contraceptive, a double barrier method, or commitment to sexual abstinence. 12) Diabetic patients must have well controlled disease. Controlled disease is considered if there has been no change in medications (oral or insulin) greater than 10% for the past 30 days. There should be no sign or symptom of ketosis at enrollment or within 30 days prior to enrollment. 13) The primary ESFT population must have a time from diagnosis to first relapse < or = 24 months, must have received at least two distinct chemotherapy programs (one for initial systemic therapy and a second for first relapse) and be surgically unresectable.
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E.4 | Principal exclusion criteria |
1) Clinically significant unrelated systemic illness (such as serious infections requiring active systemic therapy; cardiovascular disease [congestive heart failure, recent myocardial infarction, unstable angina, inadequately controlled hypertension], poorly controlled diabetes; hepatic renal or other organ dysfunction) which would, in the judgment of the treating physician, compromise the patient’s ability to tolerate the investigational agent or be likely to interfere with the study procedures or results. 2) Known hypersensitivity to any of the components of R1507 or prior hypersensitivity reactions to monoclonal antibodies (refer to section 8.3 for study drug formulation). 3) Concomitant use of any other investigational agent(s). An investigational therapy is defined as treatment for which there is currently no approved indication from regulatory authorities. Prior use of investigational agent(s) is acceptable if at least 3 weeks have elapsed since last dose and no future doses are planned. 4) Current or previous treatment (within the past 6 months) with chronic, pharmacologic doses of corticosteroids, immunosuppressive agents or medications that inactivate or may interfere with the pharmacologic activity of R1507. 5) Current or prior therapy with IGF inhibitor (monoclonal or specific kinase inhibitor). 6) Pregnant patients or patients who are breast feeding. Subjects capable of pregnancy (post menarche and not post-menopausal, defined as over 12 months since final menstrual period) must have a negative pregnancy test within 7 days prior to first dose. 7) History of solid organ transplant. 8) Other malignant disease diagnosed within the previous 5 years, excluding intra-epithelial cervical neoplasia or non-melanoma skin cancer.
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E.5 End points |
E.5.1 | Primary end point(s) |
For all Ewing’s Sarcoma Family of Tumours subgroup of patients, the primary endpoint is event-free survival. For all other histologic subgroups, the primary endpoint is response rate. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
To explore changes in PET scans in patients treated with R1507. |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The trial has a survival endpoint and therefore will continue as long as a patient having received treatment on trial survives |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |