Azenosertib in Uterine Serous Carcinoma: Biomarker Study
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexFemale
Age18+
SponsorJoyce Liu, MD
About this trial
This research study is being done to investigate how Azenosertib affects tumor cells of persistent or recurrent uterine serous carcinoma.
The name of the study drug involved in this study is:
-Azenosertib (a type of Wee1 inhibitor)
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Participants must have histologically or cytologically confirmed recurrent or persistent uterine serous carcinoma. For the purposes of this study, uterine carcinomas (with the exception of carcinosarcomas) that have any component that is considered serous will be considered a uterine serous carcinoma.
Participants must have measurable disease, defined as at least one lesion that can be accurately measured per RECIST 1.1 criteria. See Section 12 for the evaluation of measurable disease.
Participants must have had one prior platinum-based chemotherapy regimen for management of advanced or metastatic uterine serous carcinoma. Participants with early stage disease who received adjuvant platinum-based chemotherapy are also eligible if they recur within 12 months of their adjuvant therapy. Chemotherapy administered only in conjunction with primary RT as a radiosensitizer should not count as a systemic regimen. There is no restriction on the number of prior lines of therapy a participant may have previously received. Additionally, participants must have a known tumor MSI or MMR status and those participants with MSI-high or MMR-deficient tumors must have already received prior therapy with a PD1 or PD-L1 immune checkpoint inhibitor or be deemed not to be a candidate for immune checkpoint therapy.
Age 18 years or older. Because no dosing or adverse event data are currently available on the use of azenosertib in participants <18 years of age, children are excluded from this study.
Disqualifiers
Participants who have had chemotherapy, radiotherapy, or investigational therapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to first dose of azenosertib. Participants may not have had hormonal therapy within 2 weeks of the first dose of azenosertib.
Participants who have not recovered from adverse events due to prior anti-cancer therapy administered more than 3 weeks before first dose of azenosertib (e.g.,., have residual toxicities > Grade 1) with the exception of alopecia.
Participants who are receiving any other investigational agents for this condition.
Participants may not have had prior receipt of a cell cycle checkpoint inhibitor (e.g., Chek1, Wee1, or ATR inhibition)
Trial design
Design model
Single group
Treatments tested in this trial
Azenosertib
DrugWee1 inhibitor, 25mg and 100mg tablets, taken orally per protocol.
Treatment groups
25 Participants
are divided into 1 treatment groupGroup A: AzenosertibExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Percentage Change in Replication Fork Speed in Overall Response
Replication fork speed assessed by DNA fiber assays in PDO models. Responder defined as participants achieving complete response (CR) or partial response (PR) based on RECISTv1.1 criteria. Wilcoxon rank sum tests will be used to compare the percentage change in replication fork speed with exposure to WEE1 inhibition in co-clinical models between overall response responder and non-responder.
Time frame
Up to 7 months2
Percentage Change in Replication Fork Speed in 6 Month Progression Free Survival (PFS6)
Replication fork speed assessed by DNA fiber assays in PDO models. PFS6 is a binary endpoint where patients that are alive and progression free (per RECIST 1.1) at 6 months are considered responders. All other patients (those that died or progressed prior to 6 months or those with less than 6 months of follow-up for progression) are considered non-responders. Wilcoxon rank sum tests will be used to compare the percentage change in replication fork speed with exposure to WEE1 inhibition in co-clinical models between overall response responder and non-responder.
Time frame
At 6 monthsSecondary outcomes
1
Overall Response Rate (ORR)
The overall response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECISTv1.1 criteria.
Time frame
Up to 7 months2
6-month Progression-Free Survival (PFS6)
6-month PFS is a probability estimated using progression-free survival based on the Kaplan-Meier method is defined as the duration between randomization and documented disease progression (PD) or death, or is censored at time of last disease assessment.
Time frame
At 6 months3
Clinical Benefit Rate (CBR)
CBR defined as proportion of participants with Partial Response (PR) + Complete Response (CR) + Stable Disease (SD) ≥6 months per RECIST 1.1
Time frame
Up to 7 months4
Median Duration of Overall Response (DOR)
Duration of Overall Response (DOR), estimated using the Kaplan Meier method, is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) per RECISTv1.1, until the first date that recurrent or progressive disease is objectively documented. Participants without progressive disease are censored at the date of last disease assessment.
Time frame
Up to 7 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Joyce Liu, MD
Lead sponsor
Dana-Farber Cancer Institute
Sponsor institution
National Cancer Institute (NCI)
Collaborator
Zentalis
Collaborator
Source ClinicalTrials.gov