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

Completed · Phase 1

Conditions studied: Unspecified Adult Solid Tumor, Protocol Specific

In brief

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.

Key facts

Study ID: NCT02146222
Run by: University of Wisconsin, Madison
People needed: 14
Starts: 2014-09-01
Expected to finish: 2016-12-01
Last updated by the study team: 2019-11-18

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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
All patients need to be willing to undergo planned pharmacodynamic assessments, including serial PET imaging and pharmacokinetic sampling
Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; all women of childbearing potential must have a negative pregnancy test prior to receiving X-82; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Ability to understand and the willingness to sign a written informed consent document

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
The eligibility of patients taking medications that are potent inducers or inhibitors of the cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) liver enzyme will be determined following a review of their case by the principal investigator; every effort should be made to switch patients taking such agents or substances to other medications; any identified agent needs to be stopped at least 2 weeks prior to study registration
Patients with known brain metastases should be excluded; patients who had definitive treatment for their brain metastases which includes surgical resection/stereotactic body radiation therapy (SBRT) with whole brain radiation therapy (WBRT) > 6 months ago will be eligible
Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infections or psychiatric illness/social situations that would limit compliance with study requirements are ineligible
Pregnant women are excluded from this study; breastfeeding should be discontinued prior to starting study treatment
Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
Patients taking herbal supplements (St. John's Wort, gingko balboa, etc.) should discontinue these supplements two weeks prior to study registration
Patients cannot be receiving concomitant chemotherapy, radiotherapy, experimental therapy or any other therapy for the purposes of anti-cancer treatment
Subjects must not have clinically significant bleeding (i.e. GI bleed, intracranial bleeding) whtin 6 months or have had major surgery within 4 weeks. Minor surgeries (i.e. port placement, cataract surgery) are allowed if completed more than within 2 weeks from the start of treatment.
Any brain metastases must be stable and not progressing prior to study entry
Patients with prior malignancy except for the following:

Where it is running

University of Wisconsin-Carbone Cancer Center — Madison, Wisconsin, United States

Full record on ClinicalTrials.gov

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