Cabozantinib-S-Malate in Treating Patients With Advanced Solid Tumors and Human Immunodeficiency Virus
This phase I trial studies the side effects and best dose of cabozantinib-s-malate in treating patients with advanced solid tumors and human immunodeficiency virus. Cabozantinib-s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Unspecified Adult Solid Tumor, Protocol Specific
Other: pharmacological study
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Trial of Cabozantinib (XL184) for Advanced Solid Tumors in Persons With HIV Infection|
- Adverse events reported using the National Cancer Institute (NCI) CTCAE version 4.0 [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]
- Maximal tolerated dose (MTD) of cabozantinib-s-malate, graded according to the NCI CTCAE version 4.0 [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]Dose-limiting toxicity (DLT) will be defined as any cabozantinib-s-malate related grade 3 or 4 non-hematologic toxicity including grade 3 nausea and/or vomiting and grade 3 diarrhea despite prophylaxis and/or treatment or any of the following grade 4 hematologic toxicities: thrombocytopenia, neutropenia of more than 5 days duration, and neutropenia of any duration with fever or documented infection; additionally, treatment delay of 14 days or greater due to unresolved toxicity or any dose reduction required due to a cabozantinib-related adverse event will be considered a DLT.
- Response rates using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: No ]Binomial proportions and their 95% confidence intervals will be used
- Effects of therapy on HIV viral load [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: No ]A repeated measures analysis of variance will be used to assess the effect of cabozantinib-s-malate on CD4+ cell counts and HIV viral loads across time points.
- CD4+ cell counts [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: No ]A repeated measures analysis of variance will be used to assess the effect of cabozantinib-s-malate on CD4+ cell counts and HIV viral loads across time points.
- Pharmacokinetic parameters [ Time Frame: Days 1, 22, and 23 of course 1 ] [ Designated as safety issue: No ]Tabulated and descriptive statistics (e.g., geometric means and coefficients of variation) calculated for each dose level. Pharmacokinetic parameters (i.e., half life [T½], confidence intervals [Cl], and area under the curve [AUC]) will be compared across relevant antiretroviral therapies using nonparametic statistical testing techniques.
|Study Start Date:||June 2013|
|Estimated Primary Completion Date:||April 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (cabozantinib-s-malate)
Patients receive cabozantinib-s-malate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other Names:Other: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
I. To determine the safety and tolerability of cabozantinib (XL184) (cabozantinib-s-malate) as a single agent in solid tumor patients with human immunodeficiency virus (HIV) infection and to determine the maximal tolerated dose (MTD) in this patient population.
I. To investigate possible pharmacokinetic interactions between cabozantinib and antiretroviral therapy in persons with HIV infection.
II. To investigate the effects of therapy on patient immune status and HIV viral load.
III. To preliminarily assess objective response rates associated with treatment for commonly represented tumors.
OUTLINE: This is a dose-escalation study.
Patients receive cabozantinib-s-malate orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01822522
|United States, New York|
|Albert Einstein College of Medicine||Recruiting|
|Bronx, New York, United States, 10461|
|Contact: Missak Haigentz 718-920-4826 firstname.lastname@example.org|
|Principal Investigator: Missak Haigentz|
|United States, Texas|
|Baylor College of Medicine||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Elizabeth Y. Chiao 713-794-8666 email@example.com|
|Principal Investigator: Elizabeth Y. Chiao|
|Principal Investigator:||Missak Haigentz||AIDS Associated Malignancies Clinical Trials Consortium|