E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic or Advanced Non-Small-Cell Lung Cancer (NSCLC) |
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E.1.1.1 | Medical condition in easily understood language |
Metastatic or Advanced Non-Small-Cell Lung Cancer (NSCLC) |
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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 | 10025044 |
E.1.2 | Term | Lung cancer |
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 if the addition of oral veliparib to carboplatin and paclitaxel compared to carboplatin and paclitaxel alone in subjects with metastatic or advanced NSCLC
will improve progression-free survival (PFS). |
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E.2.2 | Secondary objectives of the trial |
To assess overall survival (OS), objective response rate, duration of response, chemotherapy-induced peripheral neuropathy (CIPN), safety, and tolerability. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject must be ≥ 18 years of age.
Life expectancy > 12 weeks (as per Investigator's clinical assessment).
Subject must have cytologically or histologically confirmed NSCLC.
Subject must have metastatic or advanced NSCLC (stage IIIB or IV) that is not amenable to surgical resection or radiation with curative intent at time of study Screening.
Subject must have at least 1 unidimensional measurable NSCLC lesion on a CT scan as defined by RECIST (version 1.1).
Subject must consent to provide available archived FFPE tissue sample of NSCLC lesion (primary or metastatic) for central review and biomarker analysis.
Subject must have no history of brain metastases or evidence of primary CNS tumors as demonstrated by a baseline MRI.
Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1.
Subjects with fluid retention, including ascites or pleural effusion, may be allowed at the discretion of the Investigator.
Subject must have adequate bone marrow, renal and hepatic function. |
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E.4 | Principal exclusion criteria |
Subject has a known hypersensitivity to paclitaxel or to other drugs formulated with polyethoxylated castor oil (Cremophor).
Subject has a known hypersensitivity to platinum compounds.
Subjects with peripheral neuropathy ≥ grade 2.
Subjects with a known EGFR mutation of exon 19 deletion or L858R mutation in exon 21. (Subjects with wild type EGFR, unknown status or other type of EGFR mutation will be considered eligible).
Subject has received prior systemic anti-cancer therapy for metastatic NSCLC.
Subject has received adjuvant chemotherapy ≤ 12 months prior to C1D1.
Subject has received anti-cancer Chinese medicine or anti-cancer herbal remedies within 14 days prior to C1D1.
Subject has undergone External Beam Radiation Therapy (EBRT) ≤ 8 weeks prior to C1D1.
Clinically significant and uncontrolled major medical condition(s).
Subject has previously been treated with a PARP inhibitor. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Progression Free Survival is defined as the number of days from the date the subject was randomized to the date the subject experienced a confirmed event of disease progression (as determined by the central imaging center), 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) |
Overall Survival, Objective Response Rate, Duration of Response and Chemotherapy Induced Peripheral Neuropathy |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Overall Survival - number of days from randomization to date of death
Objective Response Rate - subjects who have a partial or complete response based on assessment by central imaging read per RECIST 1.1.
Duration of Response - number of days from the day the criteria are met for complete response or partial response (whichever is recorded first) to the date that progressive disease is objectively documented by the central imaging center.
Chemotherapy-Induced Peripheral Neuropathy - scores from the EORTC QLQ-CIPN20 instrument will be evaluated and the area under the curve from baseline to Month 4 and 6 will be computed. In addition, the incidence of treatment-emergent grade 3 or 4 adverse events of peripheral neuropathy will be obtained. |
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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 | 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) | 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 | 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 | No |
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 |
Canada |
Czech Republic |
France |
Germany |
Hungary |
Puerto Rico |
Russian Federation |
Slovakia |
United States |
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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 end-of-study is defined as the date of the last subject's last visit, or last follow-up visit, whichever is longer. |
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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 | 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 |