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

Inclusion Criteria

• Patients with histologically or cytologically confirmed solid malignancy are eligible for treatment as long as insurance approval for docetaxel is obtained
• Patients with at least one target lesion amenable to serial static and dynamic FLT-PET/CT imaging will be mandated to have correlative FLT-PET/CT imaging per the study schema for a target of 20 patients with a maximum of 30 patients
• Patients may have up to three prior lines of systemic cytotoxic chemotherapy for metastatic or unresectable disease; prior use of hormonal agents (agents targeting the androgen receptor or biosynthesis pathway [goserelin, leuprolide, bicalutamide, enzalutamide, abiraterone], tamoxifen, aromatase inhibitors, fulvestrant, etc) are allowed; other hormonal agents not listed need to be reviewed by the principal investigator prior to enrollment; combination chemotherapy is considered to be a single line of chemotherapy; 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
• 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

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 =< 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; patients cannot be receiving concomitant chemotherapy, radiotherapy, experimental therapy or any other therapy for the purposes of anti-cancer treatment
• Prior anti-VEGF directed therapy may be allowed only if approved by the principle investigator (PI)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to X-82, docetaxel, or granulocyte colony stimulating factors
• 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
• Subjects must not have clinically significant bleeding (i.e. gastrointestinal [GI] bleed, intracranial bleeding) within 6 months or have had major surgery within 4 weeks; minor surgeries (i.e. port placement, cataract surgery) are allowed if completed more than 2 weeks from the start of treatment
• 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
• 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 who had treatment for their brain metastases greater than 1 month prior to treatment will be eligible; any brain metastases must be stable and not progressing prior to study entry
• Patients with prior malignancy except for the following: * Adequately treated basal cell or squamous cell skin cancer * In situ cervical cancer * Adequately treated stage I or II cancer from which the patient is currently in complete remission and has been disease free for the past 2 years * Any other cancer from which the patient has been disease-free for 5 years
• 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