This is an open-label, Phase 1 clinical study to evaluate the safety, tolerability, PK profiles, and clinical activity of IV and PO arginine supplementation + SOC chemoimmunotherapy regimens in participants with PROC.
This is a Phase I, investigator-initiated and open-label study. Patients will be evaluated and treated at University of Alabama Birmingham Hospital. Patients will receive both oral and IV arginine with the physician choice of paclitaxel, pembrolizumab, +/- bevacizumab or pembrolizumab, bevacizumab, and oral cyclophosphamide, where doses and schedule are consistent with standard of care. Patients who are excluded from the trial due to progression will be scheduled for three- and six-months follow-up evaluations after the last dose. The goal for enrollment will be 6-24 patients with a 3-patient safety dose escalation lead-in using a 3+3 enrollment model for each regimen.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
University of Alabama at Birmingham Womens & Infants Center
Birmingham, Alabama, United States
Proportion of patients with serious adverse events
This measures the proportion of patients experiencing serious adverse events
Time frame: Baseline through year 2
Overall Response Rate
Tumor burden will be evaluated in all participants by the investigator at screening and during/after the intervention period per RECIST 1.1 guidelines. Based on changes in tumor burden, participants will be classified as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or not evaluable (NE). Participants who are classified as CR or PR will be defined as responders. The overall response rate (ORR) is the proportion of responders out of the evaluable participants. ORR = (PR + CR)/(PR + CR+ SD+ PD)
Time frame: Baseline through year 2
Duration of Response
Duration of response (DOR) is a time-to-event endpoint measured only in participants who respond to treatment. DOR is the time between response to treatment and disease progression or death. Patients who are lost to follow-up before disease progression or death are censored at time of last contact.
Time frame: Baseline through year 2
Disease control rate
Tumor burden will be evaluated in all participants by the investigator at screening and during/after the intervention period per RECIST 1.1 guidelines. Based on changes in tumor burden, participants will be classified as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or not evaluable (NE). Participants who are classified as CR, PR or SD will be defined as having disease control. The disease control rate (DCR) is the proportion of participants with disease control out of the evaluable participants. DCR = (PR + CR + SD)/(PR + CR+ SD+ PD)
Time frame: Baseline through year 2
Progression Free Survival
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Continue - Weekly paclitaxel + q3w pembrolizumab +/- bevacizumab + q3w 30g IV arginine + 4.5g daily PO arginine
q3w IV bevacizumab + q3w IV pembrolizumab + daily oral phosphamide + 4.5g daily oral arginine
q3w IV bevacizumab + q3w IV pembrolizumab + daily oral phosphamide + 30mg IV arginine
q3w IV bevacizumab + q3w IV pembrolizumab + daily oral phosphamide + 30mg IV arginine + 4.5g PO arginine
Continue - q3w IV bevacizumab + q3w IV pembrolizumab + daily oral phosphamide + 30mg IV arginine + 4.5g PO arginine
Progression free survival (PFS) is a time-to-event endpoint. PFS is the time between start of treatment and the earlier of disease progression or death. Patients who are lost to follow-up before disease progression or death are censored at time of last contact.
Time frame: Baseline through year 2
Overall Survival
Overall survival (OS) is a time-to-event endpoint. OS is the time between start of treatment and death. Patients who are lost to follow-up before death are censored at time of last contact.
Time frame: Baseline through year 2