patients with platinum- and erlotinib-resistant, locally advanced or metastatic non-small-cell lung adenocarcinoma.
Conditions
Interventions
Product Code: AVE0005
Pharmaceutical Form: Concentrate for solution for infusion
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-
Sponsors
sanofi-aventis recherche & développement
Eligibility
Sex/Gender
All
Inclusion criteria
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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the overall objective response rate (ORR) of AVE0005 (VEGF Trap) 4.0 mg/kg IV every 2 weeks in this patient population.;Secondary Objective: •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);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. | — |
Countries
France
Outcome results
None listed