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A Phase 1 Study To Assess the Effect of Rifampin on the Pharmacokinetics of Linifanib in Subjects With Advanced or Metastatic Solid Tumors

Phase 1
18 Years
Not Enrolling
Advanced Solid Tumors

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Trial Information

A Phase 1 Study To Assess the Effect of Rifampin on the Pharmacokinetics of Linifanib in Subjects With Advanced or Metastatic Solid Tumors

This study is designed to explore the drug interaction between rifampin and linifanib to
determine the potential effect of rifampin on the metabolism of linifanib. Linifanib will be
taken alone or in combination with rifampin. The safety of a single dose administration of
linifanib when administered alone and in combination with rifampin will be assessed.
Subjects may enroll in a separate extension study to continue receiving linifanib after
completion of this study.

Inclusion Criteria

Inclusion Criteria

1. Age is greater than or equal to 18 years.

2. Subject must have a histologically or cytologically confirmed non-hematologic
malignancy other than HCC.

3. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2.

4. Subject must have adequate bone marrow, renal and hepatic function.

- Bone Marrow: Absolute neutrophil count (ANC) >= 1,500/mm^3 (1.5 X 10^9/L);
Platelets >= 75,000/mm^3 (75 X 10^9/L); Hemoglobin >= 9.0 g/dL (1.4 mmol/L)

- Renal function: serum creatinine <= 2.0 mg/dL (0.81 mmol/L);

- Hepatic function: AST and ALT <= 1.5 X ULN unless liver metastases are present,
then AST and ALT <= 5.0 X ULN; bilirubin <= 1.5 mg/dL (0.026 mmol/L).

5. Subject must have Partial Thromboplastin Time (PTT) ULN) and International Normalized Ratio (INR)
Exclusion Criteria

1. Subject has received anti-cancer therapy including investigational agents, cytotoxic
chemotherapy, radiation therapy or biologic therapy within 21 days or within a period
defined by 5 half lives, whichever is shorter, prior to study drug administration.
In addition subject has not recovered to less than or equal to Grade 1 clinically
significant adverse effects/toxicities of the previous therapy.

2. Subject has undergone major surgery within 21 days of Study Day 1.

3. Subject has untreated brain or meningeal metastases. Subjects with treated brain
metastases that are radiographically or clinically stable (for at least 4 weeks after
therapy) and who have no evidence of cavitation or hemorrhage in the brain lesion,
are eligible provided that they are asymptomatic and do not require corticosteroids
(must have discontinued steroids at least 1 week prior to Study Day 1).

4. Subject has received potential inhibitors of the metabolism of linifanib within 21
days prior to initial study drug administration. Such drugs include CYP3A
inhibitors, CYP1A2 inhibitors, CYP2C19 inhibitors, CYP2C8 substrates and CYP3A

5. Current enrollment in another clinical trial..

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Outcome Measure:

To investigate the effect of rifampin on the pharmacokinetic of linifanib in subjects with advanced or metastatic solid tumors.

Outcome Description:

To assess the effect of rifampin on the pharmacokinetics of linifanib and metabolite(s), an analysis will be performed for the natural logarithms of Cmax and AUC of linifanib and metabolite(s) with concentrations that permit confident determination of values of the pharmacokinetic variables. A paired t-test will be performed to compare the central value on Study Day 13 (with rifampin) to that on Study Day 1 (without rifampin). Point estimates and 90% confidence intervals will also be provided.

Outcome Time Frame:

Blood samples for the PK of linifanib will be collected at various time points from Day 1 through Day 17.

Safety Issue:


Principal Investigator

Mark D. McKee, MD

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

May 2011

Completion Date:

October 2011

Related Keywords:

  • Advanced Solid Tumors
  • Neoplasms



Site Reference ID/Investigator# 49953Tucson, Arizona  85724-5024
Site Reference ID/Investigator# 49952Madison, Wisconsin  53792