Solid Tumors
Conditions
Brief summary
This is a Phase One study to determine the safety, tolerability, and maximum tolerated dose of intravenous artesunate in patients with solid tumors. A rapid dose escalation design will be used, in which single patients will be enrolled to escalating dose levels until a grade 2 or higher toxicity occurs during cycle 1. Enrollment will then continue using 3 to 6 patients at each dose level until a dose is reached at which 2 or more patients out of 6 experience a treatment-related toxicity.
Detailed description
A rapid dose escalation design will be used, in which single patients will be enrolled to each dose level until a grade \>/= 2 treatment-related toxicity occurs during cycle 1; enrollment then will proceed using a classic 3+ 3 dose escalation design. If the toxicity was grade 2, then enrollment will continue on that dose level. If the toxicity was grade 3 or 4, then enrollment will continue on one dose level below that dose. Dose escalation with the 3+3 design will continue until \>/= 2 patients out of 6 experience a treatment-related dose-limiting toxicity. Then, the maximum tolerated dose and recommended Phase II dose of intravenous artesunate will be one dose level below the level at which the toxicities occurred.
Interventions
Intravenous Artesunate in escalating doses: 8, 12, 18, 25, 34, 45 mg/kg on days 1 and 8 of every 3 week cycles
Sponsors
United States Department of Defense
Georgetown University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least one measurable lesion by RECIST criteria * Willing to undergo pharmacogenetic testing * Over the age of 18 years and able to provide informed consent * No standard of care therapy available which has a proven overall survival benefit * Adequate kidney, liver, and bone marrow function * Life expectancy of greater than 3 months * ECOG performance status less than or equal to 2
Exclusion criteria
* Chemotherapy or surgery within 4 weeks of treatment start * Radiation treatment within 3 weeks prior to treatment start * Untreated brain metastases or neurologically unstable CNS metastases * Any severe or uncontrolled medical condition or other condition which could affect participation in the study including: unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction \</= 6 months prior to study entry * Previous diagnosis of alpha- or beta-thalassemia * Patients on a medication or herbal therapy known to inhibit CYP2A6, UGT1A9, or UGT2B7 * Female patients who are pregnant or breast feeding, or adult patients who are of reproductive potential and are unwilling to refrain from conceiving a child during study treatment * Patients unwilling or unable to comply with the protocol, or provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose | 1 year | One dose level below the dose at which 2 or more out of 6 patients experienced dose-limiting toxicities |
Countries
United States
Outcome results
None listed