A Phase 1 Study of ABT-869 in Subjects With Solid Tumors

An Open Label, Phase I Study Evaluating Pharmacokinetics, Safety, and Tolerability of ABT-869 in Subjects With Solid Tumors

The objective of this study is to evaluate the pharmacokinetics, safety and tolerability of ABT-869 in Japanese patients with solid tumors up to the Recommended Phase Two Dose that was determined in a previous the M04-710 study.

Study Overview

• Status: Completed
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: ABT-869

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Subjects aged from 20 to 75 years and ECOG PS of 0-2 at screening.
• Subject must have a solid tumor that is refractory to standard therapies or for which a standard effective therapy does not exist.
• The subject must have adequate bone marrow, renal and hepatic function.
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation and up to six months following completion of therapy.
• The subject must voluntarily sign and date an informed consent.

Exclusion Criteria

• The subject currently exhibits symptomatic or intervention indicated CNS metastasis.
• The subject has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal, biologic or any investigational therapy within 4 weeks of enrollment or has not fully recovered from toxicity resulting from past treatment(s) that affects the assessments in this study at the enrollment.

• The subject with the following conditions during screening assessment.

  1. proteinuria CTC grade > 1 as measured by urinalysis and 24 hour urine collection
  2. diastolic blood pressure (BP) > 95 mmHg; or systolic blood pressure (BP) > 150 mmHg
  3. a history of or currently exhibits clinically significant cancer related events of bleeding
  4. LV Ejection Fraction < 50%
  5. received a cumulative dose of Anthracycline > 360 mg/m2 for treatment of cancer
  6. receiving therapeutic anticoagulation therapy
  7. having fractures except for chronic bone lesion due to bone metastases
• The subject exhibits evidence of other clinically significant uncontrolled condition(s).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Dose escalation from Open label 0.05 to 0.25 mg/kg once a day dosing for 21 days	Drug: ABT-869; 2.5 mg or 10 mg tablet, Once a day, oral dose, dose per body weight (dose determined by group; 2.5mg or 10mg tablet) until evidence of uncontrolled unacceptable toxicity or disease progression. For more information, please see Arm Description.
Experimental: Group 2; Open label 0.10 mg/kg once a day dosing after safety evolution of Group 1	Drug: ABT-869; 2.5 mg or 10 mg tablet, Once a day, oral dose, dose per body weight (dose determined by group; 2.5mg or 10mg tablet) until evidence of uncontrolled unacceptable toxicity or disease progression. For more information, please see Arm Description.
Experimental: Group 3; Open label 0.20 mg/kg once a day dosing after safety evolution of Group 2	Drug: ABT-869; 2.5 mg or 10 mg tablet, Once a day, oral dose, dose per body weight (dose determined by group; 2.5mg or 10mg tablet) until evidence of uncontrolled unacceptable toxicity or disease progression. For more information, please see Arm Description.
Experimental: Group 4; Open label 0.25 mg/kg once a day dosing after safety evolution of Group 3	Drug: ABT-869; 2.5 mg or 10 mg tablet, Once a day, oral dose, dose per body weight (dose determined by group; 2.5mg or 10mg tablet) until evidence of uncontrolled unacceptable toxicity or disease progression. For more information, please see Arm Description.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety tolerability assessment	Weekly assessment for 3 weeks then every 3 weeks or more frequently as needed
Dose limiting toxicity determination	Weekly assessment for the first 3 weeks
Pharmacokinetic profile evaluation	Day 1 and Day 15

Secondary Outcome Measures

Outcome Measure	Time Frame
Preliminary tumor response	Every 6 week

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

General Publications

• Asahina H, Tamura Y, Nokihara H, Yamamoto N, Seki Y, Shibata T, Goto Y, Tanioka M, Yamada Y, Coates A, Chiu YL, Li X, Pradhan R, Ansell PJ, McKeegan EM, McKee MD, Carlson DM, Tamura T. An open-label, phase 1 study evaluating safety, tolerability, and pharmacokinetics of linifanib (ABT-869) in Japanese patients with solid tumors. Cancer Chemother Pharmacol. 2012 Jun;69(6):1477-86. doi: 10.1007/s00280-012-1846-6. Epub 2012 Mar 2.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: July 16, 2008
• First Submitted That Met QC Criteria: July 17, 2008
• First Posted (Estimate): July 18, 2008

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: Neoplasms
• Other Study ID Numbers: M10-227