E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with platinum- and erlotinib-resistant, locally advanced or metastatic non-small-cell lung adenocarcinoma. |
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MedDRA Classification |
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 determine the overall objective response rate (ORR) of AVE0005 (VEGF Trap) 4.0 mg/kg IV every 2 weeks in this patient population. |
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E.2.2 | Secondary objectives of the trial |
•To assess duration of response (DR), progression-free survival (PFS), and overall survival (OS) in this patient population •To evaluate the safety profile of IV AVE0005 (VEGF Trap) •To determine the pharmacokinetics, including population pharmacokinetics, of IV AVE0005 (VEGF Trap) •To determine the immunogenicity of IV AVE0005 (VEGF Trap) •To explore potential biological and pharmacogenomic markers of AVE0005 (VEGF Trap) activity •To assess health-related quality of life (HRQL) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically-confirmed non-small-cell lung adenocarcinoma that is locally advanced or metastatic. 2. Prior treatment with at least 2 cancer drug regimens in the advanced disease treatment setting. 3. Platinum- and erlotinib-resistant disease defined by relapse or progression of disease during or after treatment, or drug intolerance. 4. Evidence of at least one unidimensionally measurable tumor lesion by CT or MRI scan according to RECIST criteria that has not been treated with surgery or radiation therapy. 5. Eighteen years of age or older. 6. ECOG performance status ≤2. 7. Resolution of any toxic effects of prior therapy (except alopecia) to NCI CTCAE v.3.0 grade ≤1 and to baseline laboratory values as defined in inclusion criterion #8. 8. Adequate organ and bone marrow function as evidenced by: a. hemoglobin ≥9.0 g/dL b. absolute neutrophil count ≥1.5 x 10 9 /L c. platelet count ≥75 x 10 9 /L d. creatinine ≤1.5 x ULN, and either proteinuria ≤500 mg/24 hours or urine protein:creatinine ratio (UPCR) ≤1 e. AST/SGOT and ALT/SGPT ≤2.5 x ULN f. total bilirubin ≤1.5 x ULN 9. Female patients must be postmenopausal, surgically sterile, or using effective contraception. All female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to enrollment. 10. Patients must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. Informed consent must be obtained in writing for all patients prior to enrollment into the study. |
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E.4 | Principal exclusion criteria |
1. Diagnosis of squamous-cell lung cancer, or any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or for in situ carcinoma of the cervix uteri. 2. Prior treatment with a VEGF or VEGF receptor inhibitor with the exception of bevacizumab (Avastin™). 3. Anticipation of a need for a major surgical procedure (e.g., impending bowel obstruction) or radiation therapy during the study. 4. Likelihood of requiring treatment during the study period with drugs not permitted by the clinical study protocol (see Section 8.9). 5. History of hypersensitivity to any Trap agents. 6. Treatment with chemotherapy, radiotherapy, surgery, blood products, or an investigational agent within 3 weeks (6 weeks for nitrosoureas, mitomycin C, immunotherapy, or cytokine therapy) of study enrollment. 7. Uncontrolled hypertension, defined as blood pressure >150/100 mm Hg (NCI CTCAE v.3.0 grade ≥2), 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 enrollment. 8. Any of the following within 6 months prior to study enrollment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, NYHA class III or IV congestive heart failure (see Appendix A), cerebrovascular accident or transient ischemic attack, grade ≥2 peripheral neuropathy, peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, deep vein thrombosis, or other thromboembolic event. 9. History of brain metastases, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease on screening CT or MRI scan. 10. Evidence of clinically significant bleeding diathesis including hemoptysis, or underlying coagulopathy. 11. Active infection, or on antiretroviral therapy for HIV disease. 12. Patient is the investigator or any subinvestigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol. 13. Mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the study. 14. Patient unlikely to comply with protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study. 15. Refusal or inability to give informed consent to participate in the study. 16. Pregnancy or breastfeeding. 17. Other severe acute or chronic medical or psychiatric condition, or significant laboratory abnormality requiring further investigation that may cause undue risk for the patient’s safety, inhibit protocol participation, or interfere with interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study. A patient may not be enrolled in this study more than once. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the confirmed objective response according to the modified RECIST criteria, which subtracts the longest cavitation diameters from the longest diameters of cavitated target lesions. Confirmation of objective responses will be confirmed by repeat tumor imaging 4-6 weeks later. All imaging studies will be reviewed by an independent third-party core imaging laboratory. |
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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 | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
determine the immunogenicity of AVE0005 (VEGF Trap) |
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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) | 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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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 | 1 |
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 |