Clinical trial NCT02146222 (phase 1, status: completed)
Conditions: unspecified adult solid tumor, protocol specific
ICD codes: H01.009, H02.209, H02.009, H02.109, H04.209, H05.409, H10.509
Drugs: vegfr/pdgfr dual kinase inhibitor x-82, docetaxel
SMILES: [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1
Eligibility criteria:

        Inclusion Criteria:

          -  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

        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

          -  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:

               -  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