E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Previously-treated, advanced or metastatic soft tissue and Ewing’s sarcoma/peripheral primitive neuroectodermal tumor (PNET) |
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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 | 10015562 |
E.1.2 | Term | Ewing's sarcoma metastatic |
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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 | 10035639 |
E.1.2 | Term | PNET of bone metastatic |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the overall progression-free survival rate (PFS) • To evaluate the objective response rate (ORR) • To determine the time to onset of response and the duration of response • To determine overall survival (OS) • To determine the clinical benefit rate (CBR) • To evaluate the safety, tolerability, and adverse event profiles of IMC-A12 in the treatment of metastatic or advanced sarcoma; and • To assess the development of antibodies against IMC-A12 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Each patient must meet the following criteria to be enrolled in this study: 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 Protocol 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. |
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E.4 | Principal exclusion criteria |
A patient who meets any of the following criteria will be excluded from the study: 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the efficacy of IMC-A12 as a single agent, as measured by the 12-week progression-free survival rate (PFS). 12-week PFS will be measured as a binary variable. Patients will be considered “successful” if radiological evaluation performed at 12 weeks after the start of therapy indicates a response of stable disease (SD), partial response (PR) or complete response (CR) as defined by response evaluation criteria in solid tumors (RECIST). Confirmation of CP/PR is not required for this analysis. All other cases, including those who experience disease progression or death, or withdraw from the study for any reason, before the 12-week evaluation, will be considered “unsuccessful.” The binomial outcome will be independently summarized per tier, and will be presented with 95% confidence interval (CI). |
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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 | No |
E.6.7 | Pharmacodynamic | No |
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 | No |
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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |