Pharmacodynamic Study of Axitinib in Patients With Advanced Solid Malignancies

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
University of Wisconsin, Madison
ClinicalTrials.gov Identifier:
NCT00859118
First received: March 9, 2009
Last updated: September 23, 2014
Last verified: September 2014
  Purpose

The main purpose of this study is to see what changes happen to the tumors while taking the axitinib and after it is stopped (during the scheduled breaks), and what changes in the tumor may be responsible for this growth. This will be done by using a special kind of scan called an 18F-FLT PET/CT.

In addition, the investigators want to find out how the drugs are processed and distributed in the human body. The investigators will also look at how different types of cancer are affected by axitinib. The investigators will also correlate vasculature kinetics extracted from the dynamic FLT PET/CT imaging with the vasculature kinetics extracted from DCE-CT.


Condition Intervention Phase
Solid Malignancies
Drug: AG-013736
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacodynamic Study of Axitinib in Patients With Advanced Solid Malignancies

Resource links provided by NLM:


Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:
  • Determine pharmacodynamic change using FLT-PET/CT scans at baseline, during axitinib exposure and washout [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • To evaluate objective response of axitinib in patients with advanced solid malignancies. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To measure change in plasma VEGF levels, during axitinib exposure and withdrawal [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Correlate axitinib pharmacokinetics with response, unexpected toxicity, VEGF levels, and FLT-PET/CT change. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Correlate vasculature kinetics extracted from the dynamic FLT PET/CT imaging with the vasculature kinetics extracted from DCE-CT [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: February 2009
Estimated Study Completion Date: December 2014
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Schedule A Cohort 1

Axitinib 5 mg PO BID x ~2 weeks (12-14 days), followed by 1 week drug break (for cycle 1 only). After Scan#3 obtained, patients will commence with Axitinib 5 mg PO BID continuously without breaks, repeated in 3 week cycles.

Scan#1: Baseline (days -3 to 0) Scan#2: Week 2 (between days 12-14) Scan#3: Week 3 (7 days after axitinib held) Up to 10 patients will receive 2 DCE-CT scans at week 2 and 3, coinciding with the FLT-PET scans.

Drug: AG-013736
Axitinib 5 mg PO BID x ~2 weeks (12-14 days), followed by 1 week drug break (for cycle 1 only)
Other Name: Axitinib
Experimental: Schedule A: Cohort 2

Axitinib 5 mg PO BID x ~2 weeks (12-14 days), followed by 1 week drug break (for cycle 1 only). After Scan#3 obtained, patients will commence with Axitinib 5 mg PO BID continuously without breaks, repeated in 3 week cycles.

Scan#1: Week 2 (between days 12-14) Scan#2: Week 3 (2 days after axitinib held) Scan#3: Week 3 (7 days after axitinib held) Up to 10 patients will receive 2 DCE-CT scans at week 2 and 3, coinciding with the FLT-PET scans.

Drug: AG-013736
Axitinib 5 mg PO BID x ~2 weeks (12-14 days), followed by 1 week drug break (for cycle 1 only). After Scan#3 obtained, patients will commence with Axitinib 5 mg PO BID continuously without breaks, repeated in 3 week cycles.
Other Name: Axitinib

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have histologically or cytologically confirmed solid malignancy (excluding lymphoma) that is metastatic or unresectable and for which no standard therapy exists (although all solid malignancies will be enrolled, a subset will be designated for NSCL cancer will be given due to planned trials in this disease.

    • must have measurable disease
    • Must be greater than or equal to 18 years old.
    • Life expectancy of greater than 12 weeks.
    • ECOG performance status less than or equal to 2.
    • Patients must have normal organ and marrow function
    • Must be willing to undergo planned pharmacodynamic assessments, including serial PET imaging, plasma markers, and pharmacokinetic sampling.
    • Women of childbearing potential and men must use adequate form of birth (hormonal or barrier method of birth control
    • must have ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

  • Must not havehad chemotherapy, radiotherapy, experimental therapy or major surgery within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered (to grade less than or equal to 1 or baseline) from clinically significant adverse events due to agents administered more than 4 weeks earlier (alopecia and fatigue excluded).

    • Patients may not be receiving any other investigational agents.
    • Prior anti-VEGF directed therapy may be allowed only if approved by the PI
    • Must not have history of allergic reactions attributed to compounds of similar chemical or biologic composition to axitinib.
    • Must not have poorly controlled hypertension (systolic blood pressure of 140 mmHg or higher or diastolic blood pressure of 90 mmHg or higher)
  • Must not require use of therapeutic doses of coumarin-derivative anticoagulants such as warfarin, although doses of up to 2 mg daily are permitted for prophylaxis of thrombosis.

    • Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain axitinib tablets are excluded.
    • Patients with any of the following conditions are excluded:

      • Serious or non-healing wound, ulcer, or bone fracture.
      • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment.
      • Any history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry.
      • History of myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within 12 months prior to study entry.
      • History of pulmonary embolism within the past 12 months.
      • Class III or IV heart failure as defined by the NYHA functional classification system.
    • Patients without appropriate lesion on CT scan for FLT-PET/CT imaging will be excluded.
    • The eligibility of patients taking medications that are potent inducers or inhibitors of that enzyme will be determined following a review of their case by the Principal Investigator.
    • Steroid use is not recommended during axitinib treatment unless absolutely necessary
    • Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible. Patients with a history of hypothyroidism are eligible provided they are currently euthyroid.
    • Must not have known brain metastases are excluded.
    • Must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infections or psychiatric illness/social situations that would limit compliance with study requirements
    • Must not be pregnant or breastfeeding.
    • Must not be HIV-positive on combination antiretroviral therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00859118

Locations
United States, Wisconsin
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, United States, 53575
Sponsors and Collaborators
University of Wisconsin, Madison
Pfizer
Investigators
Principal Investigator: Glenn Liu, M.D. University of Wisconsin, Madison
  More Information

No publications provided

Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT00859118     History of Changes
Obsolete Identifiers: NCT00839215
Other Study ID Numbers: 08905
Study First Received: March 9, 2009
Last Updated: September 23, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Axitinib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014