E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
advanced epithelial Ovarian Cancer stage IIB-IV |
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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 | 10033162 |
E.1.2 | Term | Ovarian epithelial cancer stage II |
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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 | 10033163 |
E.1.2 | Term | Ovarian epithelial cancer stage III |
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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 | 10033164 |
E.1.2 | Term | Ovarian epithelial cancer stage IV |
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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 a safe dose of rIL-21 in combination with PLD, and to assess the efficacy of this combination in terms of overall response rate (RR).
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E.2.2 | Secondary objectives of the trial |
•To evaluate the PK of PLD and rIL-21 in subjects treated with a combination of rIL-21 and PLD •To evaluate PDs and PGs in subjects treated with a combination of rIL-21 and PLD •To assess safety of the treatment in terms of toxicity assessed through clinical adverse events and CTCAE laboratory and non-laboratory toxicities. •To assess PFS •To assess HRQL •To assess if antibodies against rIL-21 are induced during treatment
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject.) 2.Advanced epithelial OC (stage IIB-IV), histologically confirmed according to AJCC (3) 3.Persistent or progressive disease after or relapse within 1 year of completion of first line platinum-containing chemotherapy 4.At least 1 measurable lesion ≤ 5 cm in the largest diameter according to RECIST criteria or assessable disease defined as: a one-dimensional measurable lesion, mass with margins not clearly defined, lesions with both diameters 0.5 cm or less on radiographic imaging, palpable lesions under 2 cm or malignant ascites respectively combined with a 2 x UNL (in the absence of cirrhosis) of CA-125 measured within 2 weeks prior to inclusion in the trial. 5.18 years of age or above 6.ECOG performance status ≤ 2 7.Haematopoietic and renal: a.White blood cell (WBC) ≥ 2.5 x 10^9/L b.Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
c.Platelet count ≥ 100 x 10^9/L
d.Haemoglobin ≥ 6.2 mmol/L e.Lymphocytes ≥ 0.8 x 10^9/L
f.No signs of haemolytic anaemia g.Serum-creatinine ≤ 177 µmol/L 8.Hepatic a.Bilirubin ≤ 1.2 x UNL b.ALAT and ASAT/SGOT ≤ 2.5 x UNL (if liver metastasis then ≤ 4 x UNL) c.LDH ≤ 2 x UNL
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E.4 | Principal exclusion criteria |
1.More than one prior chemotherapy regimen 2.First-line chemotherapy within 1 month prior to enrolment 3.Radiotherapy less than 4 weeks prior to start of treatment for bone metastasis and less than 8 weeks for visceral metastasis 4.Previous mediastinal or left thoracic irradiation 5.Bulky disease defined as 1 or more lesions > 5 cm in the largest diameter according to RECIST criteria 6.Documented positive serologic testing for hepatitis B or C within a year prior to start of treatment 7.History of or active presence of auto-immune diseases (except vitiligo and treated pernicious anaemia) 8.History of any other active malignancy (except basal cell carcinoma of the skin and cervical cancer in situ) within 5 years prior to enrolment 9.Left ventricular ejection fraction < 0.50, determined by Multigated Acquisition (MUGA) or echocardiography 10.Cardiac disease within the last 12 months defined as: a.Decompensate heart failure (New York Heart Association (NYHA) class III or IV b.Unstable angina pectoris c.Myocardial infarction 11.Signs of CNS metastasis: either known brain metastasis or symptoms of brain metastasis 12.Known chronic infectious disease including human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS) related illness 13.Any significant systemic disease which according to the investigator could compromise the safety of the subject or interfere with the trial objectives 14.Concurrent treatment with systemic corticosteroids (topical or inhaled corticosteroid treatment is permitted) 15.Known or suspected allergy to trial product or related products 16.Previous participation (treatment) in this trial 17.Concurrent participation in any other trial with experimental therapy 18.Pregnant or the intention of becoming pregnant or not using adequate contraceptive measures (Adequate contraception includes: implants, injectables, combined oral contraceptives, hormonal IUD, sexual abstinence or vasectomised partner)
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for safety of treatment is observed toxicity assessed using the US National Cancer Institute CTCAE version 3. DLT will be recorded and MTD will be determined according to criteria described in section 5.3.3. All patients included at MTD will be used in the efficacy assessment. The primary endpoint for tumour response is overall RR measured and recorded using imaging techniques, CA-125 blood samples and pelvic examination. Tumour evaluations will be done according to RECIST (1) and GCIG criteria (2).
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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) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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 | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |