Clinical trial NCT01506934: A Study Evaluating the Bioavailability of Two Formulations of Linifanib and Food Effect on Pharmacokinetics of Linifanib in Subjects With Advanced or Metastatic Solid Tumors
Official title: A Phase 1, Open Label, Randomized, Adaptive, Cross-Over Study Evaluating the Bioavailability of Two Formulations of Linifanib and Food Effect on Pharmacokinetics of Linifanib in Subjects With Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced or Metastatic Solid Tumors
Lead sponsor: Abbott
Sponsor class: INDUSTRY
First posted: 2012-01-10
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: A pharmacokinetic study to compare 2 clinical formulations of linifanib and the effect of food on the pharmacokinetics of linifanib.

Detailed description: This study is designed to evaluate the bioavailability of linifanib from two formulations and the effect of food on the pharmacokinetics of the linifanib formulation intended for commercialization. Subjects may enroll in a separate extension study to continue receiving linifanib after completion of this study.

Eligibility 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 Hepatocellular Carcinoma (HCC).
3. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2.
4. Subject must have adequate bone marrow, renal and hepatic function as follows:

   * Bone Marrow: Absolute neutrophil count (ANC) \>= 1,500/mm3 (1.5 X 109/L); Platelets \>= 75,000/mm3 (75 X 109/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) \</= 1.5 x Upper Limit of Normal ( ULN) and International Normalized Ratio (INR) \</= 1.5.

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 Period 1, 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, Period 1).
4. Current enrollment in another clinical trial.

Primary outcomes:
measure: Calculate the Cmax and Tmax of participating subjects
timeFrame: PK parameters will be measured: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose in each study period.
Secondary outcomes:
measure: Safety: Adverse Events - The number of participants with adverse events will be reported as a measure of Safety.
timeFrame: All adverse events occuring from Day 1 of Period 1 through the Final Visit will be reported.
measure: Safety: Physical Examination and Vital Signs - Physical examination will be performed and vital signs will be assessed for participants as a measure of safety.
timeFrame: Physical exam at Screening, Day 1 of Periods 1, 2 and 3 and Day 5, Period 2 (FE portion), Day 5, Period 3 (BA Portion)/Final Visit and 30 day safety follow-up; Vital Signs (blood pressure, heart rate, body temperature) will be done at all visits.
measure: Safety: Clinical Lab Tests will be performed for each participant as a safety measure.
timeFrame: Screening, Day 1, Periods 1 and 2, Day 5, Period 2 (FE portion), Day 5, Period 3 (BA portion)/Final Visit and 30 day safety follow-up.
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Site Reference ID/Investigator# 51465
state: Maryland
city: Detroit
country: United States
facility: Site Reference ID/Investigator# 61282
state: Michigan
city: Lebanon
country: United States
facility: Site Reference ID/Investigator# 51463
state: New Hampshire
city: San Antonio
country: United States
facility: Site Reference ID/Investigator# 52122
state: Texas
Study officials:
References: