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About
This is an open label Phase 2 study to evaluate the efficacy and safety of ACR-368 as monotherapy or with ultra-low dose gemcitabine (ULDG) sensitization in participants with endometrial cancer.
Full description
OncoSignature Selected Cohorts (Arms 1 and 2):
Participants in Arms 1 & 2 will be allocated into two arms based on prospectively predicted sensitivity to ACR-368 using the OncoSignature® Companion Diagnostic test, as follows:
Arm 1: OncoSignature Positive tumors
Arm 2: OncoSignature Negative tumors
OncoSignature Unselected Cohort (Arm 3):
In Arm 3 participants will not require a biopsy or OncoSignature result.
Participants in Arm 1 will receive ACR-368 as monotherapy. Participants in Arms 2 and 3 will receive ACR-368 with ULDG sensitization. Participants in all arms will be treated until disease progression, unacceptable toxicity or any criterion for stopping the study drug or withdrawal from the trial occurs.
Enrollment
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Volunteers
Inclusion and exclusion criteria
Inclusion Criteria: General
Participant must be able to give signed, written informed consent.
Participant must have histologically documented, high-grade endometrial cancer.
Treatment History Requirements:
Participant must have histologically confirmed metastatic cancer that has progressed during or after at least 1 prior therapeutic regimen.
Participant must have at least 1 measurable lesion per RECIST v1.1 criteria (by local Investigator) in a baseline tumor imaging that has been obtained within 28 days of the treatment start. Participant must have radiographic evidence of disease progression based on RECIST v1.1 criteria following the most recent line of treatment.
Arm 1 and 2 only: Participant must be willing to provide tissue from a newly obtained tumor biopsy from an accessible tumor lesion not previously irradiated after written informed consent.
Newly obtained is defined as a specimen taken after written informed consent is obtained, during the 28-day Screening period.
Participant must be willing to provide an archival tumor tissue block or at least 20 unstained slides, if available.
Participant must have stabilized or recovered (Grade 1 or baseline) from all prior therapy related toxicities, except as follows:
Participant must have an Eastern Cooperative Oncology Group Performance Status 0 or 1.
Participant must have an estimated life expectancy of longer than 3 months.
Participant must have adequate organ function at Screening, defined as:
Participant must have adequate coagulation profile as defined below if not on anticoagulation. If subject is receiving anticoagulation therapy, then subject must be on a stable dose of anticoagulation for ≥ 1 month:
Exclusion Criteria: General
Participant with known symptomatic brain metastases requiring > 10 mg/day of prednisolone (or its equivalent). Participants with previously diagnosed brain metastases are eligible if they have completed their treatment, have recovered from the acute effects of radiation therapy or surgery prior to the start of ACR-368 treatment, fulfill the steroid requirement for these metastases, and are neurologically stable based on central nervous system imaging ≥ 4 weeks after treatment.
Participant has mesenchymal tumors of the uterus.
Participant has a history of clinically meaningful ascites, defined as history of paracentesis or thoracentesis with therapeutic intent, within 4 weeks of Screening. Subjects with planned therapeutic paracentesis or thoracentesis between Screening and Cycle 1 Day 1 dosing are excluded.
Participant had systemic therapy or radiation therapy within 3 weeks prior to the first dose of study drug.
Participants has known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection that is considered uncontrolled based on the criteria included in Appendix 2.
Participant has a history of clinically meaningful coagulopathy, bleeding diathesis.
Participant has cardiovascular disease, defined as:
Participant has a history of major surgery within 4 weeks of Screening.
Participant has experienced bowel obstruction related to the current cancer within the last 6 months or signs or symptoms of intestinal obstruction, which include nausea, vomiting, or objective radiologic finding of bowel obstruction in the last 4 weeks before the start of the treatment.
Participant has taken a prior cell cycle CHK1 inhibitor, including ACR-368
Primary purpose
Allocation
Interventional model
Masking
353 participants in 3 patient groups
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Central trial contact
Monica Phadnis; Mansoor Raza Mirza, MD
Data sourced from clinicaltrials.gov
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