Pharmacodynamic Study of Axitinib in Patients With Advanced Solid Malignancies

NCT00859118 | Completed Phase 1 DMC

• 5 other identifiers: CO 08905H-2008-0202A534260SMPH\MEDICINE\HEM-ONCNCI-2011-00744
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (2)

• Determine pharmacodynamic change using FLT-PET/CT scans at baseline, during axitinib exposure and washout

  1 year

• To evaluate objective response of axitinib in patients with advanced solid malignancies.

  1 year

Secondary Outcomes (3)

• To measure change in plasma VEGF levels, during axitinib exposure and withdrawal

  1 year

• Correlate axitinib pharmacokinetics with response, unexpected toxicity, VEGF levels, and FLT-PET/CT change.

  1 year

• Correlate vasculature kinetics extracted from the dynamic FLT PET/CT imaging with the vasculature kinetics extracted from DCE-CT

  1 year

Study Arms (2)

Schedule A Cohort 1

EXPERIMENTAL

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

Schedule A: Cohort 2

EXPERIMENTAL

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

Interventions

AG-013736 DRUG

Axitinib 5 mg PO BID x \~2 weeks (12-14 days), followed by 1 week drug break (for cycle 1 only)

Also known as: Axitinib

Schedule A Cohort 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Pfizer: collaborator

Study Sites (1)

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, 53575, United States

Location

Related Links

• University of Wisconsin Carbone Cancer Center

MeSH Terms

Conditions

Neoplasms

Interventions

Axitinib

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Glenn Liu, M.D.

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2009
• First Posted: March 10, 2009
• Study Start: February 1, 2009
• Primary Completion: May 1, 2013
• Study Completion: December 1, 2014
• Last Updated: November 19, 2019

Record last verified: 2014-12

Locations

US (1)