Pharmacodynamic Study of Axitinib in Patients With Advanced Solid Malignancies

• ClinicalTrials.gov Identifier: NCT00859118
• Recruitment Status: Completed
• First Posted: March 10, 2009
• Last Update Posted: November 19, 2019
• Sponsor: University of Wisconsin, Madison
• Collaborator: Pfizer
• Information provided by (Responsible Party): University of Wisconsin, Madison

Tracking Information

• First Submitted Date: March 9, 2009
• First Posted Date: March 10, 2009
• Last Update Posted Date: November 19, 2019
• Study Start Date: February 2009
• Actual Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 29, 2012)

• Determine pharmacodynamic change using FLT-PET/CT scans at baseline, during axitinib exposure and washout [ Time Frame: 1 year ]
• To evaluate objective response of axitinib in patients with advanced solid malignancies. [ Time Frame: 1 year ]

• Original Primary Outcome Measures (submitted: March 9, 2009): Determine pharmacodynamic change using FLT-PET/CT scans at baseline, during axitinib exposure and washout AND To evaluate objective response of axitinib in patients with advanced solid malignancies. [ Time Frame: 1 year ]

Current Secondary Outcome Measures (submitted: February 28, 2012)

• To measure change in plasma VEGF levels, during axitinib exposure and withdrawal [ Time Frame: 1 year ]
• Correlate axitinib pharmacokinetics with response, unexpected toxicity, VEGF levels, and FLT-PET/CT change. [ Time Frame: 1 year ]
• Correlate vasculature kinetics extracted from the dynamic FLT PET/CT imaging with the vasculature kinetics extracted from DCE-CT [ Time Frame: 1 year ]

• Original Secondary Outcome Measures (submitted: March 9, 2009): To measure change in plasma VEGF levels, during axitinib exposure and withdrawal AND correlate axitinib pharmacokinetics with response, unexpected toxicity, VEGF levels, and FLT-PET/CT change. [ Time Frame: 1 year ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pharmacodynamic Study of Axitinib in Patients With Advanced Solid Malignancies
• Official Title: Pharmacodynamic Study of Axitinib in Patients With Advanced Solid Malignancies

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Neoplasms

Intervention

• 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
• 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

Study Arms

• 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.

  Intervention: Drug: AG-013736
• 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.

  Intervention: Drug: AG-013736

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 9, 2009): 30
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 2014
• Actual Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00859118
• Other Study ID Numbers: CO 08905; H-2008-0202 ( Other Identifier: Institutional Review Board ); A534260 ( Other Identifier: UW Madison ); SMPH\MEDICINE\HEM-ONC ( Other Identifier: UW Madison ); NCI-2011-00744 ( Registry Identifier: NCI Trial ID )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: University of Wisconsin, Madison
• Study Sponsor: University of Wisconsin, Madison
• Collaborators: Pfizer

Investigators

• Principal Investigator: Glenn Liu, M.D.; University of Wisconsin, Madison

• PRS Account: University of Wisconsin, Madison
• Verification Date: December 2014