E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage IIIb/IV Non-Squamous Non Small-Cell Lung Cancer |
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E.1.1.1 | Medical condition in easily understood language |
late-stage non-squamous 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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029522 |
E.1.2 | Term | Non-small cell lung cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10029521 |
E.1.2 | Term | Non-small cell lung cancer stage IIIB |
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 compare the OS of patients with stage IIIb/IV non-squamous NSCLC receiving treatment with bavituximab plus docetaxel or placebo plus docetaxel |
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E.2.2 | Secondary objectives of the trial |
• To compare PFS and ORR in patients receiving treatment with bavituximab plus docetaxel or placebo plus docetaxel
• To compare safety (AEs and clinical laboratory measurements) in patients receiving treatment with bavituximab plus docetaxel or placebo plus docetaxel
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Men and women at least 18 years of age
• Histologically or cytologically confirmed and documented stage IIIb/IV non-squamous NSCLC according to the American Joint Committee on Cancer Staging Manual, 7th Edition
• Radiographic disease recurrence or progression during or after front-line, platinum-based doublet chemotherapy. For patients with known EGFR-activating mutations or ALK translocations, appropriate targeted treatment should have been used. Mutation testing is not required
• ECOG performance status of 0 or 1
• Adequate hematologic, renal, and hepatic function
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E.4 | Principal exclusion criteria |
• Squamous, small-cell, carcinoid, adenosquamous, large-cell neuroendocrine, or mixed histology containing small-cell or squamous-cell NSCLC
• Known history of bleeding disorders, eg, von Willebrand disease or hemophilia
• Cavitary tumors or tumors invading or abutting large blood vessels
• Clinically significant bleeding such as gross hematuria, GI bleeding, and hemoptysis within 6 months of screening
• Thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, arterial thrombosis) within 6 months of screening
• Grade 2 or higher peripheral neuropathy
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is OS, defined as the number of days from randomization until death, regardless of cause. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Endpoints are evaluated at each scheduled visit (please refer to Protocol section 6) |
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E.5.2 | Secondary end point(s) |
Efficacy
• PFS: number of days from randomization until either death regardless of cause, or radiologically confirmed progressive disease (PD)
• ORR: percentage of patients who achieve complete (CR) or partial (PR) response
Tumor assessments for the determination of PFS and ORR will be according to modified RECIST 1.1 as secondary endpoints. Key modifications of the RECIST 1.1 criteria will include:
• Selection of up to 10 target lesions, 5 per organ
• New non-nodal lesions < 1 cm are considered equivocal. New nodes ≥ 1 cm but < 1.5 cm in short axis are considered equivocal.
Safety
• AEs
• laboratory measurements: hematology (CBC with platelets and differential, biochemistry, and anti-drug antibodies [ADAs])
• vital signs
Population PK
• nonlinear mixed effects modeling to evaluate intrinsic (eg, age, gender, race, weight, height, etc.) and extrinsic factors (eg, smoking) that could influence bavituximab exposure and/or response
• assessments of exposure-response relationships for safety and efficacy
• assessments of the effect of body size on the PK of bavituximab
Exploratory
• Immunological studies
• Lung Cancer Symptom Scale (LCSS) at baseline, Cycles 3 and 5, every 9 weeks during maintenance therapy, and end of treatment
• Potential evidence of radiological pseudoprogression and possible flare effect in patients receiving bavituximab plus docetaxel versus placebo plus docetaxel
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Endpoints are evaluated at each scheduled visit (please refer to Protocol section 6) |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
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 | 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 | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
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 |
Belgium |
France |
Germany |
Greece |
Hungary |
Italy |
Korea, Republic of |
Romania |
Russian Federation |
Spain |
Taiwan |
Ukraine |
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 trial will end when the required number of events has been reached and the database is clean and locked for analysis. Sponsor may stop the study (and/or the study site) for any reason with appropriate notification. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |