VEGFR/PDGFR Dual Kinase Inhibitor X-82 and Docetaxel in Treating Patients With Solid Tumors

NCT02146222 | Completed Phase 1

• 5 other identifiers: UW13112NCI-2014-009442014-0528A534260SMPH\MEDICINE\HEM-ONC
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This partially randomized phase I trial studies the side effects and how well sequential dosing of vascular endothelial growth factor receptor (VEGFR)/platelet derived growth factor receptor (PDGFR) dual kinase inhibitor X-82 and docetaxel works in treating patients with solid tumors. VEGFR/PDGFR dual kinase inhibitor X-82 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving VEGFR/PDGFR dual kinase inhibitor X-82 and docetaxel one at a time instead of concurrently may work in treating patients with solid tumors.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (3)

• Incidence of toxicity graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 (Pharmacodynamic study)

  The number and severity of toxicities and adverse events will be summarized using frequencies and percentages and stratified by X-82 dose level (low or high) and treatment (X-82 alone or X-82/docetaxel). Ninety-five percent confidence intervals for the toxicity rates will be constructed.

  Up to 2 years

• Changes in the FLT PET/CT vascular parameters for VEGF/PDGF dual kinase inhibitor X-82

  The changes in FLT PET/CT parameters will be calculated and summarized using descriptive statistics and compared using a paired t-test or non-parametric Wilcoxon signed rank test.

  Baseline to day 15 (course 1)

• Changes in the FLT PET/CT vascular parameters for the combination of VEGFR/PDGFR dual kinase inhibitor X-82 and docetaxel

  The changes in FLT PET/CT parameters will be calculated and summarized using descriptive statistics and compared using a paired t-test or non-parametric Wilcoxon signed rank test.

  Day 1 to day 15 (course 2)

Secondary Outcomes (3)

• Disease response assessed by the RECIST 1.1

  Up to 2 years

• Changes in VEGF

  Baseline to up day 15 (course 2)

• Pharmacokinetic parameters of VEGFR/PDGFR dual kinase inhibitor X-82

  Within 3 hours prior to X-82 administration on days 1, 12-15, and 19-21 (course 1); and days 12-15 (course 2)

Other Outcomes (2)

• Objective response rate (ORR)

  Up to 2 years

• Incidence of toxicity graded according to NCI CTCAE version 4.0 (Dose expansion study)

  Up to 2 years

Study Arms (2)

Arm I (high dose X-82, docetaxel)

EXPERIMENTAL

Patients receive high dose VEGFR/PDGFR dual kinase inhibitor X-82 PO QD on days 2-15. Beginning course 2, patients also receive docetaxel IV over 60 minutes on day 1.

Drug: VEGFR/PDGFR dual kinase inhibitor X-82; Drug: docetaxel; Other: fluorine F 18 fluorothymidine; Procedure: positron emission tomography/computed tomography; Other: pharmacological study; Other: laboratory biomarker analysis

Arm II (low dose X-82, docetaxel)

EXPERIMENTAL

Patients receive low dose VEGFR/PDGFR dual kinase inhibitor X-82 PO QD on days 2-15 and docetaxel IV as in Arm I.

Drug: VEGFR/PDGFR dual kinase inhibitor X-82; Drug: docetaxel; Other: fluorine F 18 fluorothymidine; Procedure: positron emission tomography/computed tomography; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

VEGFR/PDGFR dual kinase inhibitor X-82 DRUG

Given PO

Also known as: X-82

Arm I (high dose X-82, docetaxel); Arm II (low dose X-82, docetaxel)

docetaxel DRUG

Given IV

Also known as: RP 56976, Taxotere, TXT

Arm I (high dose X-82, docetaxel); Arm II (low dose X-82, docetaxel)

fluorine F 18 fluorothymidine OTHER

Undergo FLT PET/CT

Also known as: 18F-FLT, 3'-deoxy-3'-[18F]fluorothymidine, fluorothymidine F-18

Arm I (high dose X-82, docetaxel); Arm II (low dose X-82, docetaxel)

positron emission tomography/computed tomography PROCEDURE

Undergo FLT PET/CT

Arm I (high dose X-82, docetaxel); Arm II (low dose X-82, docetaxel)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm I (high dose X-82, docetaxel); Arm II (low dose X-82, docetaxel)

laboratory biomarker analysis OTHER

Correlative studies

Arm I (high dose X-82, docetaxel); Arm II (low dose X-82, docetaxel)

Eligibility Criteria

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

You may qualify if:

• For the pharmacodynamic (PD) cohort, patients must have histologically or cytologically confirmed solid malignancy (excluding lymphoma) that is metastatic or unresectable; all patients will need to be approved by the principal investigator \[PI\] as certain diseases may not be appropriate for the imaging assessments)
• For the dose expansion cohort, patients with histologically or cytologically confirmed solid malignancy are eligible for treatment as long as insurance approval for docetaxel is obtained.
• Patients must have no available therapies that will confer clinical benefit and docetaxel is a reasonable treatment option for their malignancy
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \> 20 mm with conventional techniques or as \> 2 times the slice width with spiral CT scan (i.e. 10 mm if the CT slice width is 5 mm, 14 mm if the CT slice width is 7 mm)
• Life expectancy of greater than 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status: 0 or 1
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9 g/dL
• Serum calcium =\< 12.0 mg/dL
• Total serum bilirubin =\< institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal
• Creatinine =\< 1.5 mg/dL OR creatinine clearance (measured) \>= 50 mL/min
• Urinary protein =\< 2+ by urine analysis; if urine protein is \> 2+ then a 24-hour urine collection can be done and the patient may enter only if urinary protein is \< 2 g per 24 hours

You may not qualify if:

• 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 =\< 1 or baseline) from clinically significant adverse events due to agents administered more than 4 weeks earlier (alopecia and fatigue excluded); clinical significance to be determined by investigator
• Patients may not be receiving any other investigational agents
• Prior anti-VEGF directed therapy may be allowed only if approved by the PI
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to X-82 or docetaxel
• Patients with poorly controlled hypertension (systolic blood pressure of 140 mmHg or higher or diastolic blood pressure of 90 mmHg or higher) are ineligible; patients with a history of hypertension (HTN) and stable blood pressure (BP) \< 140/90 on anti-HTN regimen are eligible
• Patients will be required to have a baseline electrocardiogram (EKG) prior to the start of treatment; patients with a corrected QT (QTc) \> 480 millisecond (ms) are excluded from the study
• 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 X-82 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, ventricular arrhythmia, stable/unstable angina, symptomatic congestive heart failure, coronary/peripheral artery bypass graft or stenting or other significant cardiac disease within 12 months prior to study entry
• Any history of arterial or venous thrombosis/thromboembolic event, including pulmonary embolism within the past 12 months
• Any episode of atrial fibrillation in the prior 12 months
• Patients without appropriate lesion on CT scan for fluorothymidine (FLT)-PET/CT imaging will be excluded

Sponsors & Collaborators

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

Study Sites (1)

University of Wisconsin-Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Jackson TL, Boyer D, Brown DM, Chaudhry N, Elman M, Liang C, O'Shaughnessy D, Parsons EC, Patel S, Slakter JS, Rosenfeld PJ. Oral Tyrosine Kinase Inhibitor for Neovascular Age-Related Macular Degeneration: A Phase 1 Dose-Escalation Study. JAMA Ophthalmol. 2017 Jul 1;135(7):761-767. doi: 10.1001/jamaophthalmol.2017.1571.

  PMID: 28570723 DERIVED

Related Links

• University of Wisconsin Carbone Cancer Center

MeSH Terms

Interventions

Docetaxel; alovudine; Magnetic Resonance Spectroscopy

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Justine Bruce, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 20, 2014
• First Posted: May 23, 2014
• Study Start: September 1, 2014
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: November 18, 2019

Record last verified: 2018-02

Locations

US (1)