E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients treated with second-line docetaxel after failure of one platinum based therapy for locally advanced or metastatic non-small-cell lung cancer (NSCLC). |
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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 | 10029520 |
E.1.2 | Term | Non-small cell lung cancer stage IIIA |
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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 demonstrate overall survival (OS) improvement for aflibercept + docetaxel compared to docetaxel + placebo as second line treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). |
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E.2.2 | Secondary objectives of the trial |
-To compare efficacy of aflibercept to placebo for: • Progression Free Survival (PFS), • Response Rate (RR) as per RECIST criteria (JNCI 2000), • Health Related Quality of Life (HRQL) assessed by the Lung cancer symptom scale (LCSS) questionnaire
- To assess the overall safety of the two treatment arms.
- To assess the pharmacokinetics of intravenous (IV) aflibercept in this patient population.
- To determine immunogenicity of IV aflibercept (anti- aflibercept antibody detection) in all patients. |
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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 |
There are 2 sub-studies, i.e. pharmacokinetics and immunogenicity sub-studies, which are part of the EFC10261 study amended protocol 1 dated 2007-06-15. The objectives are the following:
• To assess the pharmacokinetics of intravenous (IV) aflibercept. Free and bound aflibercept will be measured. The ratio free aflibercept/bound aflibercept will be also estimated as an indicator of the presence of circulating endogenous VEGF.
• To determine immunogenicity of IV aflibercept.
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E.3 | Principal inclusion criteria |
- Histological/cytological proven locally advanced or metastatic non-small cell lung cancer.
- Disease progression during or after one, and only one, prior anticancer therapy which is platinum-based (chemotherapy or targeted therapy) for advanced or metastatic disease. Disease progression within 6 months of adjuvant platinum-based chemotherapy is accepted. |
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E.4 | Principal exclusion criteria |
- Related to the methodology • Squamous histology/cytology • Less than 28 days elapsed from prior treatment with radiotherapy, surgery, or chemotherapy to the time of randomization. Less than 42 days elapsed from prior major surgery (lung resection) to the time of randomization. • Prior isotope therapy, whole pelvic radiotherapy, or radiotherapy to > 25% of bone marrow • Adverse events (excluding alopecia and those listed in the specific exclusion criteria) from any prior anticancer therapy of grade >1 (National Cancer Institute Common Terminology Criteria [NCI CTCAE] v.3.0) at the time of randomization. • Age <18 years. • Eastern Cooperative Oncology Group (ECOG) performance status (PS) > 2. • History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease. • History of another neoplasm. Adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer, or any other cancer from which the patient has been disease-free for > 5 years are allowed. • Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to randomization. • Any of the following events within the 3 months prior to randomization: treatment resistant peptic ulcer disease, erosive oesophagitis or gastritis, grade 3 or 4 gastrointestinal bleeding/hemorrhage, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, or other uncontrolled thromboembolic event. • Any of the following events within the 6 months prior to randomization: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft surgery, NYHA class III or IV congestive heart failure, stroke or transient ischemic attack. • Occurrence of deep vein thrombosis within 4 weeks, prior to randomization. • Acquired immunodeficiency syndrome (AIDS-related illnesses)or known human immunodeficiency virus (HIV) disease requiring antiretroviral treatment • Any severe acute or chronic medical condition, which could impair the ability of the patient to participate to the study or interfere with interpretation of study results. • Absence of signed and dated Institutional Review Board (IRB)- approved patient informed consent form prior to enrollment into the study. • Pregnant or breast-feeding woman. Positive serum or urine pregnancy test prior to randomization. • Patient with reproductive potential (M/F) who do not agree to use accepted and effective method of contraception during the study treatment period and for at least 3 months after the completion of the study treatment.
- Related to aflibercept • History of prior discontinuation of any anti-VEGF agent due to adverse drug reaction. • Urine protein:creatinine ratio (UPCR) > 1 on morning spot urinalysis or proteinuria > 500 mg/24h. • Serum Creatinine > 1.5 x ULN (if creatinine 1.0 - 1.5 x ULN, creatinine clearance calculated according to Cockroft-Gault formula < 60 mL/min will exclude the patient). • Uncontrolled hypertension, defined as blood pressure >150/100 mm Hg (grade ≥ 2 according to NCI CTCAE v.3.0), or systolic blood pressure >180 mm Hg if diastolic blood pressure <90 mm Hg, on at least 2 repeated determinations on separate days, within 3 months prior to study randomization. • Patients on anticoagulant therapy with unstable dose of warfarin and/or having an out-of-therapeutic range INR (>3) within 4 weeks prior to randomization. • Evidence of clinically significant bleeding diathesis including hemoptysis, or underlying coagulopathy (e.g. INR>1.5 without vitamin K antagonist therapy), non-healing wound.
- Related to docetaxel • Prior docetaxel treatment. • Patients refractory to first line paclitaxel-based therapy (patients are considered refractory if their best response on treatment was Progressive Disease). • History of hypersensitivity to docetaxel, or polysorbate 80. • Inadequate organ and bone marrow function as evidenced by: − Hemoglobin < 10.0 g/dL − Absolute neutrophil count <1.5 x 109/L − Platelet count < 100 x 109/L − AST/SGOT and/or ALT/SGPT > 2.5 x ULN − Alkaline phosphatase (AP) > 5 x ULN − AST/SGOT and/or ALT/SGPT > 1.5 x ULN concomitant with AP > 2.5 X ULN − Total bilirubin > 1.0 x ULN • Contraindications to the use of corticosteroid treatment. • Symptomatic peripheral neuropathy grade > 2 (National Cancer Institute Common Terminology Criteria [NCI CTCAE] v.3.0). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival (OS) defined as the time interval from the date of randomization to the date of death due to any cause. |
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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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
Patients are treated with docetaxel |
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E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.5.1 | Number of sites anticipated in the EEA | 76 |
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 | Information not present in EudraCT |
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 |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |