This phase II trial studies how well sapanisertib works in treating patients with pancreatic neuroendocrine tumor that has spread to other places in the body (metastatic), does not respond to treatment (refractory), or cannot be surgically removed. Drugs such as sapanisertib may stop the growth or shrink tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVE: I. To evaluate overall response rate associated with sapanisertib (MLN0128 \[TAK-228\]) in patients with advanced pancreatic neuroendocrine tumors (PNETs). SECONDARY ENDPOINTS: I. To evaluate progression-free survival (PFS) associated with MLN0128 (TAK-228) in patients with advanced pancreatic neuroendocrine tumors (PNETs). II. To measure the safety and tolerability of MLN0128 (TAK-228) in patients with advanced PNETs. III. To evaluate disease control rate associated with MLN0128 (TAK-228) in patients with advanced PNETs. IV. To measure duration of response rate associated with MLN0128 (TAK-228) in patients with advanced PNETs. OUTLINE: Patients receive sapanisertib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 1 year, and then yearly for 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
13
Given PO
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
CHI Saint Vincent Cancer Center Hot Springs
Hot Springs, Arkansas, United States
PCR Oncology
Arroyo Grande, California, United States
Sutter Auburn Faith Hospital
Auburn, California, United States
Overall Response Rate
Response includes complete response (CR) and partial response (PR). CR is defined as disappearance of all lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Assessed every 3 months for the first 2 years, every 6 months for the 3rd year, then annually up to 5 years
Progression-free Survival (PFS)
PFS was defined as time from study registration to disease progression (as defined by the RECIST criteria) or to death without progression, whichever occurred first. If date of death was greater than 4 months after the date of last documented to be free of progression or if patients were alive and free of progression at the time of the analysis, patients were censored at the time of last disease assessment. If such a date was not available, patients were censored at the time of registration. Progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions is also considered progression.
Time frame: Assessed every 3 months for 2 years, every 6 months for the 3rd year, then annually up to 5 years
Disease Control Rate
Disease control rate was defined as the proportion of patients with best overall response of CR, PR, or stable disease (SD) among all eligible patients who started protocol treatment. CR is defined as disappearance of all lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. To be assigned a status of stable disease, measurements must have met the stable disease criteria at least once after study entry at a minimum interval of 8 weeks.
Time frame: Assessed every 3 months for 2 years, every 6 months for the 3rd year, then annually up to 5 years
Duration of Response
Duration of response was defined as the time from the onset of response (CR or PR, whichever status was recorded first) to first documentation of disease progression. Patients with responses but without documented disease progression were censored at the time of last disease evaluation. CR is defined as disappearance of all lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Disease progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions is also considered progression.
Time frame: Assessed every 3 months for 2 years, every 6 months for the 3rd year, then annually up to 5 years
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