This trial is investigating an intravenous (IV) medication called 9-ING-41 in combination with chemotherapy (carboplatin) for the treatment of advanced salivary gland cancers. The names of the study drug(s) involved in this study are: * 9-ING-41 (a GSK-3β inhibitor) * Carboplatin chemotherapy
This is a phase 2, open-label, non-randomized, single institution study investigating the novel glycogen synthase kinase-3 beta (GSK-3β) inhibitor 9-ING-41 in combination with carboplatin chemotherapy in patients with incurable, recurrent or metastatic salivary gland carcinomas (SGC). The U.S. Food and Drug Administration (FDA) has not approved 9-ING-41 as a treatment for any disease. Carboplatin is used as a treatment for salivary gland cancers, and is approved by the FDA for many cancer types. 9-ING-41 has been identified in other studies as a therapy to block the over-expression of the glycogen synthase kinase-3 beta (GSK-3β) protein, which is thought to be important in signaling cancer growth and to have immune properties. It is believed that GSK-3β is over-expressed in salivary gland cancers and by blocking the action of GSK-3β protein with 9-ING-41 it could slow salivary cancer cell growth that have developed resistance to prior chemotherapy exposure. The research study procedures include screening for eligibility and study treatment including evaluations and follow-up visits roughly every 3-weeks while on therapy, for up to one year as long as disease does not get worse and the drug therapy remains safe and tolerable. It is expected that about 33 people treated will take part in this research study. Actuate Therapeutics is supporting this research study by providing the study drug (9-ING-41) and funding some of the logistics of the trial that are beyond what would be considered standard of care.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
32
Intravenous infusion
Intravenous infusion
Intravenous infusion
Brigham and Women's Hospital
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Objective Response Rate (ORR)
ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Time frame: Tumor assessments were performed every 3 cycles (each cycle was 21 days), for up to 15.6 months.
Median Progression Free Survival (PFS)
PFS based on Kaplan-Meier is defined as the time from registration to the earlier of progressive disease (PD) or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.
Time frame: Tumor assessments were performed every 9 weeks for up to 20.2 months.
Median Overall Survival (OS)
Overall survival based on the Kaplan-Meier method is defined as the time from randomization to death. Participants alive are censored at the last date of contact (including lost-to-follow-up) or at the date of withdrawal of consent, if relevant.
Time frame: Up to 38.1 months
Duration of Response (DOR)
DOR is defined as the time from date of first documented confirmed objective response to date of first documented progressive disease (PD). Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.
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Time frame: Tumor assessments were performed every 3 cycles (each cycle was 21 days), for up to 15.6 months.
Number of Participants With Treatment Related Adverse Events (AE)
Number of participants with treatment-related AE is defined as the number of participants who experienced at least one AE assessed as possibly, probably, or definitely related to study treatment according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.
Time frame: AEs were assessed at Day 1 and Day 4 of each 21-day treatment cycle; assessed for up to 16.6 months.
Mean Score of Global Question 1 in University of Washington Quality of Life Questionnaire (UW-QOL)
UW-QOL Global Question 1 assessed how participants felt relative to before they developed their cancer. The mean score was calculated among all participants who provided a response to this question. Responses were recorded on a 5-point ordinal scale and transformed to a 0-100 score, where 0 = Much worse, 25 = Somewhat worse, 50 = About the same, 75 = Somewhat better, and 100 = Much better.
Time frame: Baseline and off-treatment (end-of-treatment) assessment; maximum treatment duration was 15.6 months.
Mean Score of Global Question 2 in UW-QOL
UW-QOL Global Question 2 assessed patients' health-related QOL during the past 7 days. The mean score was calculated among all participants who provided a response to this question. Responses were recorded on a 6-point ordinal scale and transformed to a 0-100 score, where 0 = Very Poor, 20 = Poor, 40 = Fair, 60 = Good, 80 = Very Good, and 100 = Outstanding.
Time frame: Baseline and off-treatment (end-of-treatment) assessment; maximum treatment duration was 15.6 months.
Mean Score of Global Question 3 in UW-QOL
UW-QOL Global Question 3 assessed patients' overall QOL during the past 7 days. The mean score was calculated among all participants who provided a response to this question. Responses were recorded on a 6-point ordinal scale and transformed to a 0-100 score, where 0 = Very Poor, 20 = Poor, 40 = Fair, 60 = Good, 80 = Very Good, and 100 = Outstanding.
Time frame: Baseline and off-treatment (end-of-treatment) assessment; maximum treatment duration was 15.6 months.