E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
metastatic non-squamous non-small-cell lung cancer |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025055 |
E.1.2 | Term | Lung cancer non-small cell stage IV |
|
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 addition of NTG patches to bevacizumab containing chemotherapy (experimental arm) improves PFS in patients with stage IV non-squamous NSCLC, compared to bevacizumab containing chemotherapy without NTG (control arm) |
|
E.2.2 | Secondary objectives of the trial |
Objective response rate (ORR) and disease control rate (DCR), Duration of response, OS, Safety. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically/cytologically proven stage IV non-squamous NSCLC (according to IASLC staging 7.0) • No prior chemotherapy or therapy with systemic anti-tumor therapy (e.g., monoclonal antibody therapy) or prior exposure to agents directed at the HER axis (e.g. EGFR TK inhibitors, Herceptin). Prior surgery and/or localized palliative irradiation is permitted provided that the irradiated lesion is not the only measurable lesion. Prior adjuvant chemotherapy > 1 year ago and prior treatment with an EGFR-TKI for patients with an activating EGFR mutation is allowed. • Age ≥ 18 years. • ECOG Performance Status of 0 – 2. • Life expectancy of at least 12 weeks. • Subjects with at least one uni-dimensional(for RECIST) measurable lesion. • Adequate bone marrow, liver and renal function (see protocol for details). • Adequate non-hormonal contraception for females of childbearing potential during the study and in the 6 months thereafter. • Adequate contraception for male participants (or their partners) during the study and in the 6 months thereafter. |
|
E.4 | Principal exclusion criteria |
• Clinically significant (i.e. active) cardiovascular disease: congestive heart failure >NYHA class 2; CVA or myocardial infarction < 6 months prior to study entry; uncontrolled hypertension (blood pressure systolic > 150 mmHg and/or diastolic > 100 mmHg). • Symptomatic hypotension. • History of hemoptysis at least grade 2 (bright red blood of at least 2,5 ml in the last 3 months) • Evidence of tumor invading major blood vessels on imaging (i.e. superior vena cava or pulmonary artery). • History of HIV infection or chronic hepatitis B or C. • Active clinically serious infection • Symptomatic metastatic brain or meningeal tumors. Patients with brain metastasis may be included the patient is treated with brain radiotherapy and asymptomatic. • History of organ allograft. • Patients with evidence or history of bleeding diathesis. • Non-healing wound or ulcer. • History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrolment • Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study entry • Radiotherapy within 4 weeks of start of study drug. Palliative radiotherapy for bone lesions is allowed > 14 days of start of chemotherapy. Major surgery within 4 weeks of start of study. • Use of vasodilators (including 5-fosfodiesterase inhibitors, calcium antagonists or nitrates) • Autologous bone marrow transplant or stem cell rescue within 4 months of study • Investigational drug therapy outside of this trial during or within 4 weeks of study entry • Pregnancy or lactation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival. |
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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 | No |
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 | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
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 | 20 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |