This phase I/II trial studies the side effects and best dose of nab-sirolimus and how well it works when given together with pazopanib hydrochloride in treating participants with nonadipocytic soft tissue sarcomas that has spread to other places in the body (advanced). Nab-sirolimus and pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
OUTLINE: This is a phase I, dose-escalation study of nanoparticle albumin-bound rapamycin followed by a phase II study. Participants receive nab-sirolimus intravenously (IV) on days 1 and 8 or day 1 only and pazopanib hydrochloride orally (PO) daily on days 1-21. Cycles repeat every 21 days until unequivocal clinical disease progression, unacceptable toxicity, or until in the opinion of the investigator the patient is no longer benefiting from therapy, or at the patient's discretion. After completion of study treatment, participants are followed up at 30 days, then every 12 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
19
Given IV
Given PO
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
The Maximum-tolerated Dose (MTD) of Nab-rapamycin in Combination With Pazopanib (Phase I) - Nab-Rapamycin Dose
Will be estimated using dose-limiting toxicities (DLTs). Will use a Simon's minimax design.
Time frame: First 2 cycles (3-week cycles, 21 days each)
The Maximum-tolerated Dose (MTD) of Nab-rapamycin in Combination With Pazopanib (Phase I) - Pazopanib Dose
Will be estimated using dose-limiting toxicities (DLTs). Will use a Simon's minimax design.
Time frame: First 2 cycles (3-week cycles, 21 days each)
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
A DLT is defined as any Grade 3 or greater adverse event (AE), at least possibly related to either or both nab-sirolimus and pazopanib. Only toxicities with a clearly identified and documented alternative explanation may be deemed non-DLT. Dose-limiting toxicities include any death not clearly due to underlying disease or extraneous causes, or persistent intolerable nonhematologic AE of any grade that requires dose reduction or permanent discontinuation of the study drug, in the opinion of the investigator.
Time frame: First 2 cycles (3-week cycles, 21 days each)
Dose Limiting Toxicities
A Dose-limiting toxicity is defined as any Grade 3 or greater adverse event (AE), at least possibly related to either or both nab-Sirolimus or pazopanib. Only toxicities with clearly identified and documented alternative explanation may be deemed non-DLT. Dose-limiting toxicities include any death not clearly due to underlying disease or extraneous causes, or persistent intolerable nonhematologic Ae of any grade that requires dose reduction or permanent discontinuation of the study drug, in the opinion of the investigator.
Time frame: First 2 cycles (3 week cycles, 21 days each)
Progression-free Survival (PFS) Rate
Will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 where progression is defined as a 20% increase in the sum of the longest diameter of target lesions where the sum must also demonstrate an absolute increase of at least 5 mm, or the appearance of new lesions. Will be assessed via descriptive statistics.
Time frame: At 3 months
Incidence of Adverse Events Profile
Treatment-related adverse events (AEs) experienced by participants evaluated by Common Terminology Criteria for Adverse Events (CTCAE) 5.0 and determined to be possibly related, probably related, or definitely related to either nab-sirolimus therapy, pazopanib therapy, or both.
Time frame: Up to 30 days after last dose (an average of 41 weeks)
Median PFS
Will be assessed using RECIST v1.1. Will be assessed via descriptive statistics.
Time frame: At 6 months
Progression-Free Survival Rate
Will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Will be assessed via descriptive statistics.
Time frame: At 6 months
Median Overall Survival (OS)
Will be summarized using descriptive statistics.
Time frame: At 12 months
Overall Survival
Will be assessed using descriptive statistics.
Time frame: 12 months
Objective Response Rate (CR + PR)
Will be based on RECIST v1.1. Will be evaluated by CT imaging.
Time frame: Up to 2 years
Disease Control Rate (Complete Response [CR] + Partial Response [PR] + Stable Disease [SD])
Will be based on RECIST v1.1evaluated by computed tomography (CT) imaging. Per RECIST V1.1, Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>= 30% decrease in the sum of diameters of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD).
Time frame: at 24 weeks
Duration of Response
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Will be evaluated by CT imaging.
Time frame: Up to 2 years