E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Newly diagnosed, untreated Stage III or IV high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer |
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E.1.1.1 | Medical condition in easily understood language |
Ovarian cancer or ovarian neoplasm |
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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 |
The primary objective of the study is to evaluate whether progression-free survival (PFS) is prolonged when veliparib is added to standard platinum-based chemotherapy and then continued as maintenance in the BRCA-deficient, HRD and whole populations. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives include evaluations of overall survival, safety and Disease Related Symptom scores in the BRCA-deficient, HRD and whole populations. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenetic and pharmacodynamic substudy - optional blood and tissue tests respectively |
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E.3 | Principal inclusion criteria |
"Subject must be ≥ 18 years of age
High-grade serous adenocarcinoma
Willing to undergo testing for gBRCA
Eastern Cooperative Oncology Group performance status of 0, 1, or 2" |
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E.4 | Principal exclusion criteria |
"Following histologic cell types are ineligible: endometrioid adenocarcinoma, carcinosarcoma, undifferentiated carcinoma, mixed epithelial adenocarcinoma, adenocarcinoma not otherwise specified, mucinous adenocarcinoma, clear cell adenocarcinoma, low-grade serous adenocarcinoma, or malignant Brenner's tumor.
Synchronous primary endometrial cancer, or a past history of endometrial cancer.
Prior radiotherapy to any portion of the abdominal cavity or pelvis
Clinically significant uncontrolled condition(s), including but not limited to: Bowel obstruction or gastric outlet obstruction.
History or evidence upon physical examination of central nervous system (CNS) disease." |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival in the BRCA-deficient, HRD and whole populations. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PFS will be defined as the number of days from the date that the subject was randomized to the date the subject experiences an event of disease progression, according to RECIST criteria version 1.1 (as determined by the Investigator) or to the date of death (all causes of mortality) if disease progression is not reached. |
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E.5.2 | Secondary end point(s) |
The secondary efficacy analyses for OS will be measured in the BRCA-deficient, HRD and whole populations. PFS will also be compared as a secondary analysis. Other secondary analyses will include safety and Disease Related Symptom (DRS) scores in the BRCA-deficient, HRD and whole populations. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
OS timepoint evaluation:
OS will be defined as the number of days from the day the subject is randomized to the date of the subject's death.
DRS Scores:
The overall mean change from baseline for the DRS scores will be measured at each assessment point up to 2 years or disease progression.
Safety:
The safety of veliparib will be assessed by evaluating study drug exposure, adverse events, serious adverse events, all deaths, as well as changes in laboratory determinations and vital sign parameters. Subjects who were randomized but did not receive study drug will not be included in the analyses of safety. |
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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 | Yes |
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) | 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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 | No |
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 |
Australia |
Brazil |
Israel |
Japan |
Korea, Republic of |
New Zealand |
United States |
Denmark |
Poland |
Spain |
United Kingdom |
Argentina |
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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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The global end-of-study is defined as the date of the last subject's last visit, or the date of the last subject's last follow-up contact, whichever is later. The sponsor may also end the study upon confirmation that the primary endpoint was statistically met. |
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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 | 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 |