Randomized, placebo-controlled, double-blind Phase 1b/2 study of U3-1287 (AMG 888) in combination with erlotinib in EGFR treatment naïve subjects with advanced non-small cell lung cancer (NSCLC) who have progressed on at least one prior chemotherapy.

• Conditions: Treatment for advanced or metastatic NSCLC in combination with erlotinib in subjects who are epidermal growth factor receptor (EGFR) treatment naïve after failure of at least one prior chemotherapy regimen; MedDRA version: 14.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: PTClassification code 10029521Term: Non-small cell lung cancer stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-021082-74-IT
• Lead Sponsor: DAIICHI SANKYO PHARMA DEVELOPMENT

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-12-29
• Last Update Posted: 2 June 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 210

Inclusion Criteria

Subjects must satisfy all of the following criteria to be included in the study: 1. Men or women ³ 18 years old. 2. Histologically or cytologically confirmed NSCLC with either: - Metastatic disease (Stage IV) OR - Stage IIIB disease not amenable to surgery or curative intent. 3. Disease progression or recurrence following treatment after last chemotherapy or chemoradiation regimen (completed within the previous 12 months)documented by radiographic assessment. 4. Measurable disease per RECIST guidelines Version 1.1. 5. Eastern Cooperative Oncology Group (ECOG)performance status 0 or 1. 6. Hematological function, as follows: - Absolute neutrophil count (ANC)³ 1.5´ 109/L - Platelet count ³ 100 ´ 109/L - Hemoglobin ³ 9 g/dL. 7. Renal function, as follows: - Calculated creatinine clearance³ 60 mL/min using the modified Cockroft-Gault equation or serum creatinine Are the trial subjects under 18? no
Number of subjects for this age range: 0
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

1. Left ventricular ejection fraction (LVEF) < 45%. 2. Prior EGFR-targeted regimen, anti-HER2, anti-HER3, or anti-HER4 therapy. 3. More than 2 prior chemotherapy regimens for this indication (Phase 2 subjects only). 4. History of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated with no evidence of disease for³ 5 years. 5. History of corneal disease. 6. History of interstitial lung disease. 7. Clinically active brain metastases, defined as untreated symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Subjects with treated brain metastases that are no longer symptomatic and require no treatment with steroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 4 weeks (2 weeks for subjects with a solitary brain lesion amenable to sterotactic radiosurgery) must have elapsed between the end of radiotherapy and study enrollment. 8. Uncontrolled hypertension (diastolic > 100 mmHg or systolic > 140 mmHg). It is permissible for the subject to receive treatment with antihypertensive medication to maintain blood pressure within required parameters. 9. Clinically significant electrocardiogram (ECG) changes that obscure the ability to assess the RR, PR, QT, QTc, and QRS intervals. 10. Ascites or pleural effusion requiring chronic medical intervention. 11. Myocardial infarction within 1 year before enrollment, symptomatic congestive heart failure (New York Heart Association >Class II), unstable angina, or unstable cardiac arrhythmia requiring medication. 12. Treatment with anticancer therapy, antibody-based therapy, retinoid therapy, or hormonal therapy within 4 weeks before study drug treatment or treatment with nitrosoureas or mitomycin C within 6 weeks before study drug treatment or treatment with small molecule tyrosine kinase inhibitors(TKIs) within 2 weeks before study drug treatment. Prior and concurrent use of hormone replacement therapy is permitted. 13. Therapeutic radiation therapy or major surgery within 4 weeks before study drug treatment or palliative radiation therapy within 2 weeks before study drug treatment. Radiation treatment to all sites of measureable disease unless progression is documented after radiation. No target lesion should be selected within the previously irradiated field unless there was progression at that lesion following radiation. 14. Participated in clinical drug trials within 4 weeks (2 weeks for small molecule TKIs) before study drug treatment. Current participation in other investigational procedures. 15. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection. 16. History of hypersensitivity to any of the study drugs or to any excipients. 17. Concurrent use of CYP3A4 inducers or inhibitors. 18. Any known pre-existing condition including substance abuse that could interfere with subjectâ??s participation in and completion of the protocol.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified