E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Brain metastases from NSCLC |
|
E.1.1.1 | Medical condition in easily understood language |
Brain metastases from Non-small cell lung cancer |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006128 |
E.1.2 | Term | Brain metastases |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess whether the addition of Veliparib when given during whole brain radiation therapy (WBRT) improves Overall Survival (OS) for subjects with brain metastases from Non-small Cell Lung Cancer (NSCLC). |
|
E.2.2 | Secondary objectives of the trial |
To assess Safety, Response Rate of Brain Metastases at 4 months, Time to Intracranial Progression (Radiographic), and Time to Clinical Brain Metastasis Progression. Also to evaluate whether addition of twice daily oral Veliparib during WBRT delays deterioration of neurological symptoms, delays functional decline, and improves subject quality of life. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject must be ≥ 18 years of age;
Subject must have cytologically or histologically confirmed NSCLC;
Subject must have brain metastases as demonstrated on a MRI brain scan;
Subject must be eligible for WBRT; |
|
E.4 | Principal exclusion criteria |
Subject was diagnosed with brain metastasis ≥21 days prior to Treatment Day 1;
Subject received any prior form of cranial radiation and/or neurosurgery for brain metastasis;
Subject has a Karnofsky Performance Score (KPS) of < 70;
Subject has a GPA Score of ≤ 1.0;
Subject has significant dyspnea requiring supplemental oxygen therapy;
Subject has liver metastases (restaging is not required for known liver metastasis);
Subject has more than 2 sites (organ systems) of metastases from NSCLC with the exception of the following: intra-cranial sites of metastasis from NSCLC, thoracic sites of metastasis from NSCLC, and bone metastasis;
Subject has leptomeningeal metastases or subarachnoid spread of tumor as demonstrated on a baseline MRI brain scan;
Subject's last dose of chemotherapy or investigational therapy was ≤ 7 days prior to Treatment Day 1;
Subject has unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or prior anti-cancer treatment;
Subject has a known seizure disorder that is uncontrolled, or has seizures occurring greater than or equal to 3 times a week over the past month. Subjects presenting with symptoms of seizures from the brain metastasis are eligible however he/she should receive adequate anti-seizure medication prior to study treatment;
Subject is pregnant or lactating;
Subject has previously been treated with a PARP inhibitor as an investigational agent;
Subject has clinically significant and uncontrolled major medical condition(s) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for this study is Overall Survival |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Overall Survival for a given subject will be defined as the number of days from the date the subject was randomized to the date of the subject's death |
|
E.5.2 | Secondary end point(s) |
Best Tumor Response Rate will be defined as the proportion of subjects with a complete or partial response determined by the central imaging vendor based on the bi-dimensional criteria;
Time to Intracranial Progression (radiographic) will be defined as the number of days from the date the subject was randomized to the date the subject experienced an event of radiographic progression (intracranial) determined by the central imaging vendor;
Time to Clinical Brain Metastasis progression will be defined as the number of days from the date of randomization to the date of earliest neurological deterioration (signs and symptoms) as determined by the Event Review Board |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Clinical Brain Metastasis progression defined as the number of days from the date of randomization to the date of earliest metastasis progression. All metastasis progression is included regardless of whether the subject has discontinued taking the drug. If no metastasis progression, the data will be censored at the date of last neurological assessments. If the subject has no post baseline neurological assessments, then the subject will be censored at the date of randomization
Overall Survival:Time to death is defined as the number of days from the date of randomization to the subject's death. All events of death are included, regardless of if the subject has discontinued taking the drug. If a subject has not died, then the data will be censored at subject's last known alive date. |
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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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
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) | 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 | 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 | Yes |
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 | 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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
Argentina |
Australia |
Belgium |
Brazil |
Canada |
Chile |
Czech Republic |
Egypt |
Finland |
Korea, Republic of |
Norway |
Portugal |
Puerto Rico |
Russian Federation |
Spain |
Taiwan |
Ukraine |
United States |
|
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-study is defined as when the subject has experienced either radiographic or clinical brain metastasis progression (whichever occurs last). The Month 24 study visit will be considered the last study visit for subjects who do not experience both radiographic and clinical brain metastasis progression. |
|
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 | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |