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

Information source: University of Wisconsin, Madison
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Unspecified Adult Solid Tumor, Protocol Specific

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

Phase: Phase 1

Status: Recruiting

Sponsored by: University of Wisconsin, Madison

Official(s) and/or principal investigator(s):
Justine Bruce, MD, Principal Investigator, Affiliation: University of Wisconsin, Madison

Overall contact:
Cancer Connect, Phone: (800) 622-8922, Email: cancerconnect@uwcarbone.wisc.edu

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.

Clinical Details

Official title: Pharmacodynamic Study Using FLT-PET/CT in Patients With Advanced Solid Malignancies Treated With a Sequential Combination of X-82 and Docetaxel

Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

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

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

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

Secondary outcome:

Disease response assessed by the RECIST 1.1

Changes in VEGF

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

Detailed description: PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of intermittent X-82 (VEGFR/PDGFR dual kinase inhibitor X-82) when administered in a 2 week on, 1 week off schedule (Cycle #1). II. To evaluate the safety and tolerability of intermittent X-82 administered in combination with docetaxel every 3 weeks (Cycle #2). III. To determine the change in vascular parameters using 3'Deoxy-3'-fluorothymidine (FLT) positron emission tomography (PET)/computed tomography (CT) to X-82 alone (Cycle #1). IV. To determine the change in vascular parameters using FLT PET/CT to X-82 in combination with docetaxel (Cycle #2). SECONDARY OBJECTIVES: I. To determine the objective response using Response Evaluation Criteria In Solid Tumors (RECIST) 1. 1 of intermittent X-82 with docetaxel. II. To measure the change in plasma vascular endothelial growth factor (VEGF) levels with changes on FLT PET/CT. III. To measure changes in X-82 pharmacokinetics with changes on FLT PET/CT. TERTIARY OBJECTIVES: I. To evaluate the safety and tolerability of sequential X-82 with docetaxel in disease sub-populations. (Dose expansion cohort) II. To evaluate the objective response rate of sequential X-82 with docetaxel in these disease sub-populations. (Dose expansion cohort) OUTLINE: Patients are randomized to 1of 2 treatment arms. ARM I: Patients receive high dose VEGFR/PDGFR dual kinase inhibitor X-82 orally (PO) once daily (QD) on days 2-15. Beginning course 2, patients also receive docetaxel intravenously (IV) over 60 minutes on day 1. ARM II: Patients receive low dose VEGFR/PDGFR dual kinase inhibitor X-82 PO QD on days 2-15 and docetaxel IV as in Arm I. In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. EXPANSION COHORT: Patients receive VEGFR/PDGFR dual kinase inhibitor X-82 as in Arm I and docetaxel IV over 60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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 must have histologically or cytologically

confirmed breast cancer, non-small cell lung cancer, prostate cancer, gastric cancer, or sarcoma; in addition, patients with other histologically or cytologically confirmed solid malignancy could be eligible for the orphan disease cohort if 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) > 450 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

Locations and Contacts

Cancer Connect, Phone: (800) 622-8922, Email: cancerconnect@uwcarbone.wisc.edu

University of Wisconsin-Carbone Cancer Center, Madison, Wisconsin 53792, United States; Recruiting
Cancer Connect, Phone: 800-622-8922, Email: cancerconnect@uwcarbone.wisc.edu
Jennifer Heideman, BSN, Email: Phase1@medicine.wisc.edu
Justine Yang Bruce, M.D., Principal Investigator
Additional Information

Starting date: September 2014
Last updated: April 9, 2015

Page last updated: August 23, 2015

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