| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10066697 |
| E.1.2 | Term | Ovarian cancer recurrent |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
| To compare QoL in patients treated with trabectedin/PLD vs. other platin containing combination therapy of carboplatin+ PLD, carboplatin + gemcitabine, or carboplatin + paclitaxel |
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| E.2.2 | Secondary objectives of the trial |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Women aged ≥ 18 years
2. Patients with histologically confirmed diagnosis of epithelial ovarian cancer, primary peritoneal carcinoma or fallopian tube cancer who received ≥1 prior chemotherapy
3. Patients must be eligible for platin-containing therapy; Patient is defined as platin-sensitive when considered for platin-containing therapy by the investigator. The time frame from end of prior therapy until disease progression alone is not pivotal.for study participation. Patients without a platin-containing regimen in the previous line who are also eligible for platin-containing regime are also appropriate for participation
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
5. Adequate baseline organ function as defined as
6. Leucocytes > 3.0 x 109/l
7. platelet count > 100 x 109/l
8. Absolute neutrophil count (ANC) ≥1500/mm3
9. Haemoglobin ≥ 9 g/dl
10. Alkaline Phosphatase (AP) ≤ 2.5 × ULN (consider hepatic isoenzymes 5 nucleotidase or gamma glutamyl transpeptidase (GGT), if the elevation could be osseous in origin)
11. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN
12. Creatinine-Clearance ≥ 60 ml/min (MDRD formula or Cockroft & Gault formula)
13. Serum creatinine ≤ 1.5 mg/dl
14. Creatine phosphokinase (CPK) ≤ 2.5 × ULN
15. Total bilirubin < ULN
16. Women of childbearing potential should use contraceptives or abstain from heterosexual activity for the course of the study through 6 months after the last dose of study medication or be surgically sterile.
17. Adequate cardiac function defined as left ventricular ejection fraction (LVEF) ≥ 50% as determined by echocardiogram
18. Patients must provide written informed consent prior to performance of study specific procedures or assessments, and must be willing to comply with treatment and follow up assessments and procedures. |
|
| E.4 | Principal exclusion criteria |
1. Only malignancies, which influence the prognosis
2. Any unstable or serious concurrent condition (e.g. active infection requiring systemic therapy).
3. Chemotherapy or radiation therapy or tumor embolization within 2 weeks prior to the first dose of study drug or planned during study participation.
4. Patients who have refractory disease. Refractory disease is defined if relapse occurs <4 months after beginning of platin-containing therapy.
5. Hypersensitivity to the active substance or to any of the excipients of study drug
6. Findings from ECG and/or assessment of LVEF which indicate an anthracycline-related cardiotoxic process which contradicts administration of liposomal doxorubicin or trabectidin in accordance with the requirements of the SmPCs.
7. Biological therapy, immunotherapy, hormonal therapy or treatment with an investigational agent within 14 days (for bevacizumab, 30 days) prior to the first dose of study drug.
8. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
9. Participation in another clinical study with experimental therapy within the 30 days before start of and during treatment. Participation in a non-interventional study should be discussed with sponsor and NC beforehand.
10. Patients in a closed institution according to an authority or court decision (AMG § 40, Abs. 1 No. 4)
11. Patients who are depending on the sponsor/CRO or investigational site as well as on the investigator.
12. Pregnancy or lactation period, or planning to become pregnant within 7 months after the end of treatment. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Primary Endpoint is the observation of change in QoL. This is measured for every patient as the change from baseline (C1 D1) to end of treatment (EOT) visit (3-4 weeks after C6 D1 or, in case of progression/relapse, 3-4 weeks after day 1 of last treatment Cycle). The primary QoL measure is the mean score of the Trial Outcome Index (TOI). The TOI is based on selected items from the EORTC QLQ-C30 version 3.0 and QLQ-OV28 (TOI-QLQ-OV) and includes the C-30 functional scales physical and role functioning, the symptom scales constipation, diarrhea, nausea and vomiting, in addition to the first 24 items of the EORTC Ovar 28 (i.e. all items of the EORTC Ovar 28, excluding sexual functioning). The primary endpoint will be analysed by general linear models for paired samples. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| to be measured 3 weeks after end of treatment (3-4 weeks after C6 D1 or, in case of progression/relapse, 3-4 weeks after day 1 of last treatment Cycle) |
|
| E.5.2 | Secondary end point(s) |
Clinical benefit rate (CR, PR, SD), or PD in patients with measurable disease
Difference in QoL for all other time points not included in primary endpoint
Progression-free survival (PFS)
Overall survival (OS)
Time to next medical intervention |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Clinical benefit rate (CR, PR, SD), or PD in patients with measurable disease
Difference in QoL for all other time points not included in primary endpoint
Progression-free survival (PFS) defined as the time from randomization to the first occurrence of progression or recurrence, as determined by the investigator using CT criteria, or death from any cause
Overall survival (OS), defined as the time from randomization to death from any cause
Time to next medical intervention (e.g. chemotherapy, immunotherapy) |
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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 | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | Yes |
| 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 | Yes |
| 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.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 20 |
| 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
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Regular end of study treatment is 3-4 weeks after D1C6 or earlier after progression. EOT means end of the active part of the trial. Centers perform follow-up starting with EOT (after regular termination or progression) after 6 and 12 months after baseline.
The extended follow-up phase starts for all patients after the mandatory 1 y follow-up. This phase ends when the study will be terminated, which is defined as the time point when the last patient has completed the mandatory 1 year follow-up. |
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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 | |
| E.8.9.1 | In the Member State concerned months | 52 |
| E.8.9.1 | In the Member State concerned days | |
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