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

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

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.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Linifanib; Drug: Linifanib; Drug: Carboplatin; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

General Publications

• Horinouchi H, Yamamoto N, Nokihara H, Horai T, Nishio M, Ohyanagi F, Horiike A, Nakagawa K, Terashima M, Okabe T, Kaneda H, McKee MD, Carlson DM, Xiong H, Tamura T. A phase 1 study of linifanib in combination with carboplatin/paclitaxel as first-line treatment of Japanese patients with advanced or metastatic non-small cell lung cancer (NSCLC). Cancer Chemother Pharmacol. 2014 Jul;74(1):37-43. doi: 10.1007/s00280-014-2478-9. Epub 2014 May 8.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (ACTUAL): June 1, 2012
• Study Completion (ACTUAL): June 1, 2012

Study Registration Dates

• First Submitted: September 28, 2010
• First Submitted That Met QC Criteria: October 19, 2010
• First Posted (ESTIMATE): October 21, 2010

Study Record Updates

• Last Update Posted (ACTUAL): November 21, 2017
• Last Update Submitted That Met QC Criteria: November 17, 2017
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: W12-076