Pharmacodynamic Study With FLT-PET/CT in Patients With Prostate/Other Solid Malignancies Treated With High Dose Axitinib

Pharmacodynamic Study Using FLT-PET/CT in Patients With Prostate and Other Solid Malignancies Treated With an Interrupted High-dose Axitinib Schedule

The main purpose of this study is to learn more about the safety of an investigational drug, axitinib. An investigational drug is a drug that has not been approved by the Food and Drug Administration (FDA) and is available for research use only. Researchers will also 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. This scan is considered an investigational type of scan and is not used for clinical care. These scans are not approved by the FDA, their use in this study is just for research purposes.

In addition, the investigators want to find out how the drug is processed and distributed in the human body. The investigators will also look at how different types of cancer are affected by axitinib.

Study Overview

• Status: Completed
• Conditions: Solid Malignancies; Metastatic Castrate-resistant Prostate Cancer
• Intervention / Treatment: Drug: axitinib

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed solid malignancy (excluding lymphoma) that is metastatic or unresectable and for which no standard therapy exists.
• Patients must have measurable disease
• Must be >/= 18 years of age
• All patients need to be willing to undergo planned pharmacodynamic assessments, including serial PET imaging, plasma markers, and pharmacokinetic sampling.

Exclusion Criteria:

• Patients who have had 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 -Patients may not be receiving any other investigational agents.
• Patients with prior anti-VEGF directed therapy may be allowed only if approved by the PI and greater than 8 weeks since last exposure
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to axitinib
• Patients with poorly controlled hypertension
• Patients who require use of therapeutic doses of coumarin-derivative anticoagulants
• Patients with any condition that impairs their ability to swallow and retain axitinib tablets are excluded.
• Patients with any of the following conditions are excluded: Serious or nonhealing 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
• CYP3A4 inducers/inhibitors medications will be reviewed by the Principal Investigator.
• Steroid use is not recommended during axitinib treatment
• Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible.
• Patients with known brain metastases should be excluded
• HIV-positive patients on combination antiretroviral therapy are ineligible

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Safety cohort; 6 evaluable patients with RECIST measurable solid malignancies will be enrolled to establish the safety and toxicity of axitinib at 7 mg PO BID days 1-14 in 21 day cycles.	Drug: axitinib; 7 mg PO BID days 1-14 in 21 day cycles.
Experimental: Pharmacodynamic cohort; PD cohort A: Up to 6 patients with metastatic castrate-resistant prostate cancer (evidence of soft-tissue metastases amendable to FLT-PET/CT imaging), and PD cohort B: Up to 12 patients with other solid malignancies (evidence of radiographic metastases amendable to FLT-PET/CT imaging) will be enrolled with scans obtained at baseline, peak exposure, and peak withdrawal of axitinib, in cycle#1, with repeat imaging in select patients in PD cohorts A and B at a later cycle of therapy.	Drug: axitinib; 7 mg PO BID days 1-14 in 21 day cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacodynamic change on FLT-PET/CT	baseline, cycle 1 weeks 2 and 3, pre-cycle 3, cycle 3 weeks 2 and 3

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: Pfizer
• Investigators: Principal Investigator: Glenn Liu, M.D., University of Wisconsin, Madison

Publications and helpful links

Helpful Links

• University of Wisconsin Carbone Cancer Center

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: February 22, 2012
• First Submitted That Met QC Criteria: February 27, 2012
• First Posted (Estimate): February 28, 2012

Study Record Updates

• Last Update Posted (Actual): November 19, 2019
• Last Update Submitted That Met QC Criteria: November 15, 2019
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Axitinib
• Other Study ID Numbers: CO10907; A534260 (Other Identifier: UW Madison); SMPH\MEDICINE\HEM-ONC (Other Identifier: UW Madison); 2011-0575 (Other Identifier: Institutional Review Board); NCI-2012-00142 (Registry Identifier: NCI Trial ID)