E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Germ cell tumors (GCT) including testicular and non-central nervous system (non-CNS) extragonadal types. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10061184 |
E.1.2 | Term | Germ cell cancer |
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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 |
The primary objective is to determine the objective response rate (ORR) after 4 cycles of therapy with ARQ 197 in subjects with GCT. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are the following: - To determine the progression free survival (PFS) rate at 12 weeks from enrollment. - To determine the median overall survival among subjects treated with ARQ 197. - To determine the safety and tolerability of ARQ 197 in this subject population. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must satisfy all of the following criteria to be included in the clinical study. 1. Histologically-confirmed non-CNS GCT, both seminomas and nonseminomas are allowed. 2. Male subjects 16 years of age or older. 3. Eastern Cooperative Oncology Group (ECOG) performance status ≤1. 4. Documented progression during or following ≥ 1 prior platinum-containing chemotherapy regimen(s) (no limit to number of lines of prior treatment), and considered platinum-resistant by the Investigator. Subjects who have progressed or whose tumors have recurred after stem cell transplantation are also allowed. 5. All subjects must have either declined or not be a candidate for curative therapy. In general, this means a subject would have to have progressive disease (PD) after receiving high-dose chemotherapy, have certain features making them ineligible for high-dose chemotherapy, or have refused high-dose chemotherapy despite being informed of its curative potential. 6. Subjects must have radiographically measurable disease as defined by RECIST 1.1 and meet one of the following criteria: · Documented germ cell tumor progression based on radiographic measurements; · Elevated serum tumor markers in case of radiographically measured stable disease. 7. Subjects should be able to provide written informed consent, comply with protocol visits and procedures, be able to take oral medication, and not have any active infection or chronic co-morbidity that would interfere with therapy. 8. Subjects must agree to use double-barrier contraceptive measures or avoidance of intercourse during the study and for 90 days after the last dose of study drug. 9. Adequate bone marrow, liver, and renal functions, defined as: · Platelet count ≥ 75 × 109/L · Hemoglobin ≥ 9.0 g/dL · Absolute neutrophil count (ANC) ≥ 1.5 × 109/L · Total bilirubin ≤ 2.5 mg/dL · Alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) ≤ 2.5 × upper limit of normal (ULN) (≤ 5 x ULN for subjects with liver metastases) · Serum creatinine ≤1.5 × ULN 10. Subjects must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign and date an Independent Ethics Committee or Institutional Review Board-approved informed consent form (including Health Insurance Portability and Accountability Act authorization, if applicable) before performance of any study-specific procedures or tests. |
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E.4 | Principal exclusion criteria |
Potential subjects who meet ANY of the following exclusion criteria are not eligible for enrollment into this clinical study. 1. Previous or concurrent cancer that is distinct from GCT in primary site or histology, EXCEPT treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated ≥ 3 years prior to enrollment is permitted. 2. History of cardiac disease: · Congestive heart failure defined as Class II to IV per New York Heart Association classification; · Active coronary artery disease; · Previously diagnosed bradycardia or other cardiac arrhythmia defined as ≥ Grade 2 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, or uncontrolled hypertension; · Myocardial infarction that occurred within 6 months prior to study entry (myocardial infarction that occurred > 6 months prior to study entry is permitted). 3. Active clinically serious infection(s) defined as ≥ Grade 2 according to NCI CTCAE, version 4.0. 4. Known metastatic brain or meningeal tumors, unless the subject is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of first dose of study drug and is clinically stable (no concomitant therapy, including supportive therapy with steroids or anticonvulsant medications) with respect to the tumor at the time of first dose of study drug. 5. Any primary CNS GCT. 6. Concurrent treatment with anticancer therapies including cytotoxic chemotherapy, immunotherapy, radiotherapy, vaccines or investigational therapy during the study or within 3 weeks of first dose of study drug. 7. Any major surgical procedure within 3 weeks prior to first dose of study drug. 8. Prior therapy with c-MET inhibitors, including ARQ 197. 9. Substance abuse or medical, psychological or social conditions that may, in the opinion of the Investigator, interfere with the subject’s participation in the clinical study or evaluation of the clinical study results. 10. Any condition that is unstable or that could jeopardize the safety of the subject and the subject’s protocol compliance, including known human immunodeficiency virus, hepatitis B virus or hepatitis C virus infection. 11. Inability to swallow oral medications. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the ORR of subjects treated with ARQ 197, after 4 cycles of therapy. |
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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 | Yes |
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 | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 |