E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
• Phase Ib: To establish the safety and tolerability of weekly dosed L-Annamycin in monotherapy in subjects with STS with lung metastases. • Phase II: To determine the efficacy of L-Annamycin in subjects with STS with lung metastases
|
|
E.2.2 | Secondary objectives of the trial |
Phase Ib/II: To determine further safety and tolerability for L-Annamycin, the pharmacokinetics of L-Annamycin and its metabolite (annamycinol) and efficacy. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The subject is ≥18 years old at the time of signing informed consent. 2. The subject has an ECOG performance status ≤2 with an estimated life expectancy of greater than three months. 3. The subject has a pathologically confirmed diagnosis of STS (including the following pathological subtypes: liposarcoma, leiomyosarcoma, synovial sarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma, myxofibrosarcoma, malignant peripheral nerve sheath tumour, malignant solitary fibrous tumour, and pleomorphic RMS), and documented lung metastases that are considered eligible for chemotherapy and not eligible for potentially curative surgical resection. 4. The subject must have measurable disease in the lung, defined as, at a minimum, one lesion that can be accurately measured in at least one dimension of >10 mm. Subjects with the extra-pulmonary disease are eligible. 5. The subject had prior anthracycline therapy (cumulative dose of ≤450 mg/m2) for their disease and has shown the progression of the disease before study entry – for phase II trial maximum of three previous lines of therapy (adjuvant/neoadjuvant regimen is counted as one line of systemic treatment)
|
|
E.4 | Principal exclusion criteria |
1. The subject has any condition that, in the opinion of the Investigator, places the subject at unacceptable risk if they were to participate in the study. 2. Metastases to the central nervous system 3. The subject has left ventricular ejection fraction (LVEF) <50%, valvular heart disease, or severe hypertension not controlled by medical therapy. Cardiac subjects with a New York Heart Association classification of 3 or 4 will be excluded, as will those with recent (≤ 6 months) myocardial infarction, unstable angina, or symptomatic congestive heart failure. The subject has a baseline QT/QTc interval >480 msec, a history of additional risk factors for torsade des pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) and use of concomitant medications that significantly prolong the QT/QTc interval. 4. The subject has clinically relevant serious comorbid medical conditions including, but not limited to active infection, known positive status for human immunodeficiency virus and/or active hepatitis B or C, cirrhosis, or psychiatric illness/social situations that would limit compliance with study requirements. 5. The subject is pregnant, lactating, or not using adequate contraception. 6. The subject has a known allergy to study drug or excipients. 7. The subject is required to use moderate or strong inhibitors and inducers of cytochrome P450 (CYP) family enzymes CYP3A and CYP2B and transporters that cannot be held three days before treatment and on the day of treatment.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Phase Ib: to determine the Recommended Phase 2 Dose (RP2D) • Phase II: to evaluate 3-month Progression-Free Survival (PFS).
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Phase Ib/II: To determine further safety and tolerability for L-Annamycin, the pharmacokinetics of L-Annamycin and its metabolite (annamycinol) and efficacy. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
|
this is difficult to define as it is dependent on the last MTD visit |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
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 | 6 |