This phase I trial studies the side effects and the best dose of navitoclax when given together with sorafenib tosylate in treating patients with solid tumors that have returned (relapsed) or do not respond to treatment (refractory). Navitoclax and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of the combination of navitoclax and sorafenib tosylate (sorafenib) in patients with advanced solid tumors. (Dose escalation cohort) II. To better characterize the toxicity profile of the combination of navitoclax and sorafenib. (Dose expansion cohort) SECONDARY OBJECTIVES: I. To identify any activity of this treatment combination in patients with metastatic cancer. (Dose escalation cohort) II. To seek preliminary evidence of activity of this treatment combination in patients with hepatoma. (Dose expansion cohort) CORRELATIVE OBJECTIVES: I. To determine whether the combination of navitoclax and sorafenib induces apoptosis that can be detected by peripheral blood biomarker analysis. (Dose escalation cohort) II. To assess peripheral blood biomarkers and pharmacokinetics in a more homogenous population. (Dose expansion cohort) III. To determine whether treatment is associated with Mcl-1 down regulation in hepatocellular carcinoma (HCC) at the maximum tolerated dose (MTD). (Dose expansion cohort) IV. To assess in a preliminary fashion whether pretreatment tumor cell levels of Mcl-1 predict response to this regimen through serial biopsies. (Dose expansion cohort) OUTLINE: This is a dose-escalation study of navitoclax. Patients receive navitoclax orally (PO) once daily (QD) on days 1-21 (days 1-28 cycle of 1 only) and sorafenib tosylate PO twice daily (BID) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
29
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, United States
Mayo Clinic in Florida
Jacksonville, Florida, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States
M D Anderson Cancer Center
Houston, Texas, United States
Maximum tolerated dose (MTD) of navitoclax
Will be defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4.0.
Time frame: 28 days
Incidence of adverse events
Will be graded per NCI CTCAE v. 4.0. The number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion.
Time frame: Up to 3 months
Tumor response
Will be assessed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1. Response will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease. The waterfall plot may be used to display best tumor response. Exploratory analysis of the relationship between response and other clinical endpoints may be performed.
Time frame: Up to 3 months
Time until any treatment related toxicity
The data on time-related variables will be summarized descriptively.
Time frame: Up to 3 months
Time until treatment related grade 3+ toxicity
The data on time-related variables will be summarized descriptively.
Time frame: Up to 3 months
Time until hematologic nadirs (white blood cell, absolute neutrophil count, platelets)
The data on time-related variables will be summarized descriptively.
Time frame: Up to 3 months
Time to progression
The data on time-related variables will be summarized descriptively.
Time frame: Up to 3 months
Time to treatment failure
The data on time-related variables will be summarized descriptively.
Time frame: From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 months
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