E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Epithelial ovarian cancer (including fallopian tube and primary peritoneal) |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061328 |
E.1.2 | Term | Ovarian epithelial cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10016180 |
E.1.2 | Term | Fallopian tube cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 of this study is to determine whether abiraterone has clinical activity (objective response rate assessed by imaging and/or CA125 tumour marker changes in the blood) in patients with epithelial ovarian cancer (EOC) that has relapsed within 12 months of last treatment. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are: 1) To evaluate the objective response rate (i.e. the proportion of patients with complete or partial response at 12 weeks) using RECIST criteria. 2) To evaluate objective response rate (i.e. the proportion of patients with complete or partial response at 12 weeks) using GCIG criteria (CA125 tumour marker). 3) To evaluate the proportion of patients with complete or partial response or stable disease at 12 weeks as defined by RECIST/GCIG criteria (the clinical benefit rate). 4) To evaluate the Progression Free Survival. This will be measured from the date of trial registration until first date of either death or confirmed progressive disease according to RECIST/GCIG criteria. 5) To evaluate the proportion of study participants alive and progression free at 6 months (six month progression free survival). 6) To evaluate the Time to Progression. This will be measured from the date of trial registration until the date of confirmed progressive d |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Patients must have histologically or cytologically confirmed epithelial ovarian, fallopian tube (FT) or primary peritoneal (PP) cancer and have progressed (radiological or CA125 criteria) within 12 months of last systemic anti-cancer therapy 2) Life expectancy of at least 12 weeks 3) Post-menopausal defined as: • Aged ≥ 18 years having had bilateral salpingo-oophorectomy (BSO) • Aged ≥ 45 years with intact uterus and amenorrhoeic for at least 12 months • FSH >40 U/L in patients who have had a hysterectomy and ovaries are intact (i.e. not had bilateral oophorectomy) Documentary evidence is required for patients who have undergone irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy 4) ECOG performance status of 0-2 5) Patients must not have had prior hormone therapy (e.g. tamoxifen, aromatase inhibitor, progestogens, anti-androgens) 6) Patients will have received at least one line of prior platinum-based chemotherapy 7) Measurable or evaluable disease (if not measurable by RECIST v1.1 criteria, patients must be evaluable by GCIG CA125 criteria) 8) Archival tumour tissue (FFPE or 8-10 unstained slides) must be available. Otherwise, a biopsy must be carried out to obtain sufficient tissue for histological assessment 9) Haematological and biochemical indices within acceptable ranges (as specified in the protocol) 10) Aged 18 years or over 11) Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up
|
|
E.4 | Principal exclusion criteria |
1) Tumours of mucinous, clear cell, malignant mixed mesodermal (MMMT) or non-epithelial ovarian cancers (e.g. Brenner tumours, Sex-cord tumours) 2) Radiotherapy (except for palliative reasons) or chemotherapy within the preceding three weeks (four weeks for investigational agent or within five half-lives of the investigational agent, whichever is longer) 3) Persistent grade 2 or greater toxicities from any cause except for alopecia or grade 2 peripheral neuropathy 4) Known leptomeningeal involvement or brain metastases 5) Clinical and/or biochemical evidence of hyperaldosteronism or hypopituitarism 6) Unresolved bowel obstruction 7) Major surgery within four weeks prior to commencement of trial treatment 8) Treatment with warfarin. Patients on warfarin for DVT/PE can be converted to LMWH at least one week prior to commencement of trial treatment 9) At high medical risk because of non-malignant systemic disease including active uncontrolled infection 10) Known to be serologically positive for hepatitis B and/or hepatitis C 11) Active or uncontrolled autoimmune disease that may require corticosteroid therapy 12) History of clinically significant heart disease, e.g. myocardial infarction or arterial thrombotic event within six months, severe or unstable angina, or New York Heart Association Class III or IV heart disease 13) Systolic blood pressure >160 mm Hg and diastolic blood pressure >95 mm Hg documented on at least two different occasions [Note: Hypertension controlled by antihypertensive therapy is permitted]. 14) Any other active malignancy requiring treatment 15) Patients for whom treatment with prednisone or prednisolone is contraindicated 16) Patients participating in or planning to participate in another interventional clinical trial. Participation in an observational trial is acceptable 17) Any other condition which, in the Investigator’s opinion, would not make the patient a good candidate for the clinical trial.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is to determine the objective response rate according to combined RECIST/GCIG criteria at 12 weeks after the start of treatment. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint will assessed 12 weeks from the start of treatment.
A formal interim analysis will be conducted after the first 26 patients have been on study for at least 12 weeks. |
|
E.5.2 | Secondary end point(s) |
The secondary endpoints are: • The proportion of patients with objective response according to RECIST • The proportion of patients with objective response according to GCIG (CA125) • Clinical benefit rate according to RECIST/GCIG criteria at 12 weeks • Progression Free Survival (PFS) • 6-month PFS • Time to Progression (TTP) • Overall survival (OS) • Toxicity according to CTCAE version 4.0
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Patients will continue on trial treatment until disease progression and will be followed up until 28 days (+/- 2 days) following the last administration of abiraterone. Patients will then be followed up for survival status every three months.
The IDMC will meet regularly (every 3-6 months) to monitor the progress of the trial andd assess safety. |
|
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 | 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 | Yes |
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 | 3 |
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 | 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
|
The end of the trial is defined as the date of last data capture. |
|
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 | 11 |
E.8.9.1 | In the Member State concerned days | 29 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 29 |