A Randomized Study comparing placebo and U3-1287 (AMG888) in combination with erlotinib in treatment of subjects with advanced non-small cell lung cancer who have progressed on at least one prior chemotherapy

Phase 1

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: 14.0 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.0 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.0 Level: PT Classification code 10029521 Term: Non-small cell lung cancer stage IIIB System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2010-021082-74-GB

Lead Sponsor: DAIICHI SANKYO DEVELOPMENT LTD.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 222

Inclusion Criteria

1. Men or women = 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) = 1.5 × 10e9/L
- Platelet count = 100 × 10e9/L
- Hemoglobin = 9 g/dL.

7. Renal function, as follows:
- Calculated creatinine clearance = 60 mL/min using the modified Cockroft-Gault equation or serum creatinine = 1.5 x ULN.

8. Hepatic function, as follows:
- Aspartate aminotransferase (AST) = 2.5 ×upper limit of normal (ULN) (if liver
metastases are present, < 5 × ULN)
- Alanine aminotransferase (ALT) = 2.5 ×ULN (if liver metastases are present,
< 5 × ULN)
- Alkaline phosphatase = 2.5 × ULN (if bone or liver metastases are present, < 5 × ULN)
- Bilirubin = 1.5 × ULN.

9. Prothrombin time (PT) and partial thromboplastin time (PTT) = 1.5 × ULN.

10. Availability of recent (before treatment start) or archival (does not have to be provided by treatment start) tumor specimen (Phase 2 subjects only).

11. For female subjects, must be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile, or must use maximally effective birth control during the period of therapy, and be willing to use contraception for 6 months following the last investigational drug dose and have a negative urine or serum pregnancy test upon entry into this study if female subjects of childbearing
potential.

12. For male subjects, must be surgically sterile or willing to use a double barrier contraception method upon enrollment, during the course of the study, and for 6 months following the last investigational drug dose.

13. Subjects must be competent and able to comprehend, sign, and date an Independent Ethics Committee- or Institutional Review Board-approved
Informed Consent Form (including Health Insurance Portability and Accountability Act
authorization, if applicable) before performance of any study-specific procedures or tests.
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

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 for = 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 reatment 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 stereotactic 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 reatment. Radiation treatment to all sites of measureable disease unless progression is
documented after radiation. No target lesion should be selected within the reviously 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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method