Artesunate in Treating Patients With Solid Tumors
This phase I trial studies the side effects and best dose of artesunate in treating patients with solid tumors. Artesunate may help treat cancer caused by the human papillomavirus.
Inclusion Criteria
- Solid tumor malignancy for which no standard of care therapy is available which has a proven overall survival benefit
- At least one measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
- Willing to undergo pharmacogenetic testing
- Hemoglobin >= 8.0 gm/dL
- Absolute neutrophil count (ANC) >= 1500 cells/mm^3
- Platelet count >= 100,000 /mm^3
- Creatinine within institutional normal limits or Glomerular filtration rate (GFR) > 50 mL/min/m^2 (calculated by the Cockcroft-Gault equation), calculated as follows: * For males = ((140 – age[years]) x (body weight [kg]))/((72) x (serum creatinine [mg/dL])) * For females = 0.85 x male value
- Total bilirubin =< 1.5 times upper limit of normal (ULN)
- Aspartate transaminase AST (SGOT) and alanine aminotransferase ALT (SGPT) =< 2.5 times the ULN except in patients with hepatic metastases for whom AST and ALT must be < 5.0 times the ULN
- Life expectancy of greater than 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- For expansion cohort: metastatic platinum-refractory cervical cancer, or metastatic/recurrent platinum-refractory HPV-positive head and neck cancer (as determined by polymerase chain reaction (PCR), in situ hybridization (ISH), or p16 immunohistochemistry (IHC); platinum refractory is defined as recurrent disease within 6 months after receiving cisplatin or carboplatin with radiation for their newly diagnosed disease, or after receiving cisplatin or carboplatin for their recurrent/metastatic disease
Exclusion Criteria
- Chemotherapy or surgery within 4 weeks prior to treatment start
- Radiation treatment within 3 weeks prior to treatment start
- Untreated brain metastases or neurologically unstable central nervous system (CNS) metastases
- Any severe or uncontrolled medical condition or other condition that could affect participation in this study, including: unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction =< 6 months prior to study entry
- Previously diagnosis of alpha- or beta-thalassemia since these patients may have significantly higher PK levels than patients without these disorders
- Patients on a medication or herbal therapy known to inhibit cytochrome P450 (CYP)2A6, UGT1A9, or UGT2B7
- Female patients who are pregnant or breast feeding, or adults 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
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02353026.
PRIMARY OBJECTIVES:
I. To determine the safety, tolerability, and maximum tolerated (MTD) dose of intravenous artesunate in patients with solid tumors.
SECONDARY OBJECTIVES:
I. To determine the clinical activity, including the response rate and disease control rate, of intravenous artesunate in patients with solid tumors.
II. To explore the clinical activity of intravenous artesunate in an expansion cohort of patients (n=6) with cervical or head and neck cancer caused by the Human Papillomavirus (HPV).
III. To explore the association of genetic polymorphisms in enzymes and transporters which may mediate artesunate disposition with artesunate pharmacokinetics (PK) and observed toxicities.
IV. In an exploratory manner, to correlate measures of iron (Fe), transferrin receptor, and transporters known to mediate iron homeostasis levels in tumor specimens with response to treatment.
OUTLINE: This is a dose-escalation study.
Patients receive artesunate intravenously (IV) over 5 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationMedStar Georgetown University Hospital
Principal InvestigatorJohn Frederick Deeken
- Primary IDPro00000028
- Secondary IDsNCI-2013-00689
- ClinicalTrials.gov IDNCT02353026