A Study of Linifanib (ABT-869) in Combination With Carboplatin/Paclitaxel in Japanese Subjects With Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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The primary objective of this study is to assess the safety and pharmacokinetics of linifanib, and identify tolerable dose of linifanib (ABT-869) in combination with carboplatin and paclitaxel in Japanese subjects with advanced or metastatic non-small cell lung cancer (NSCLC). Secondary objective is to obtain a preliminary efficacy of anti-tumor activity in the subjects as first-line treatment.

Official Title
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A Phase 1 Study of Linifanib (ABT-869) in Combination With Carboplatin/Paclitaxel in Japanese Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) as First-Line Treatment

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Linifanib
* Drug: Linifanib
* Drug: Carboplatin
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria The subject must be 20 and older years of age. The subject must have cytologically or histologically confirmed non-squamous NSCLC. Subjects may have a mixed histology but must be predominantly non-squamous to be eligible. The subject must have advanced or metastatic (Stage IV [According to American Joint Committee on Cancer (AJCC) staging manual, 7th edition]) disease that is not amenable to surgical resection or radiation with curative intent. The subject must have not received prior chemotherapy for NSCLC. The subject has measurable disease, defined as at least 1 unidimensionally measurable lesion on a CT scan as defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. The subject has an Easter Cooperative Oncology Group (ECOG) Performance Score of 0-1. The subject must have adequate bone marrow, renal and hepatic function. Exclusion Criteria The subject has hypersensitivity to paclitaxel or to other drugs formulated with polyethoxylated castor oil (Cremophor). The subject has received any anti-cancer therapy for treatment of NSCLC including investigational agents, immunotherapy, traditional Chinese medicine/herbal remedies, hormonal, targeted agents (i.e., erlotinib, imatinib), biologic therapy or cytotoxic chemotherapy (i.e., alkylating agents, microtubule inhibitors, antimetabolites). The subject has a history of another active cancer within the past 5 years except cervical cancer in situ, in situ carcinoma of the bladder, squamous cell or basal cell carcinoma of the skin. The subject has active ulcerative colitis, Crohn's disease, celiac disease or any other conditions that interfere with absorption. The subject has a medical condition, which in the opinion of the study investigator places them at an unacceptably high risk for toxicities. The subject is pregnant or breast feeding. The subject has NSCLC with a predominant squamous cell histology.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br> | Drug: Linifanib<br>* Low dose linifanib (once a day)<br>* Other names: ABT-869;Drug: Carboplatin<br>* Given on Day 1 of every 21-day cycle<br>* Other names: Paraplatin;Drug: Paclitaxel<br>* Given on Day 1 of every 21-day cycle<br>* Other names: Taxol;|
| Experimental: Arm B<br> | Drug: Linifanib<br>* High dose linifanib (once a day)<br>* Other names: ABT-869;Drug: Carboplatin<br>* Given on Day 1 of every 21-day cycle<br>* Other names: Paraplatin;Drug: Paclitaxel<br>* Given on Day 1 of every 21-day cycle<br>* Other names: Taxol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (Number of patients with adverse events and/or dose-limiting toxicities) | Evaluation of vital signs, physical exams, clinical lab testing and adverse event monitoring. | At each treatment visit (weekly for 6 weeks, then every 3 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preliminary tumor response | Computed Tomography (CT) scan | Week 6 | 
| Preliminary tumor response | Computed Tomography (CT) scan | Week 12 | 
| Preliminary tumor response | Computed Tomography (CT) scan | Week 18 | 
| Preliminary tumor response | Computed Tomography (CT) scan | Week 24 | 
| Preliminary tumor response | Computed Tomography (CT) scan | Week 30 | 
| Preliminary tumor response | Computed Tomography (CT) scan | Week 36 | 
| Preliminary tumor response | Computed Tomography (CT) scan | Week 42 | 
| Preliminary tumor response | Computed Tomography (CT) scan | Week 48 | 
| Preliminary tumor response | Computed Tomography (CT) scan | Week 54 |