The purpose of this study is to learn about the safety and tolerability of Cirtuvivint in combination with Olaparib in platinum resistant ovarian cancer. The study also aims to determine the recommended dose of the combination therapy. If a participant is a good fit for the study, and they enroll in the study, they will: * Visit the clinic often at the beginning of the study for physical exams, blood draws, vital signs, and other study and routine care procedures. After the first two months participants will visit the clinic every 28 days. * Take the study medications, Cirtuvivint and Olaparib. Participants will take Olaparib every day. Participants will either take Cirtuvivint 5 days per week or 2 days per week.
This trial is a non-comparative phase I combination trial with the goal of determining the safety and RP2D of cirtuvivint when given orally daily (5 days on 2 days off) combined with olaparib given orally BID (continuously) for 28 day cycles, and of cirtuvivint when given orally daily (2 days on 5 days off) combined with olaparib given orally BID (continuously) for 28 day cycles. Patients will enter the two cohorts in alternating fashion by time of enrollment. The patient population will be women with platinum resistant high grade serous or endometrioid epithelial ovarian cancer who are germline or somatic BRCA/HRD positive. Due to potential survival detriment of late line PARP inhibition, patients will be limited to no more than 3 prior lines of therapy. Olaparib will be dosed at the standard recommended dose of 300mg BID and adjusted appropriately for known adverse events.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Cirtuvivint (SM08502) is a first in class pan CDC-like kinase (CLK) and dual specificity tyrosine kinase (DYRK) inhibitor with suspected multiple anti-tumor mechanisms of action, including Wnt inhibition.
NCI Definition - A small molecule inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) with potential chemosensitizing, radiosensitizing, and antineoplastic activities. Olaparib selectively binds to and inhibits PARP, inhibiting PARP-mediated repair of single strand DNA breaks; PARP inhibition may enhance the cytotoxicity of DNA-damaging agents and may reverse tumor cell chemoresistance and radioresistance. PARP catalyzes post-translational ADP-ribosylation of nuclear proteins and can be activated by single-stranded DNA breaks.
CU Medicine Clinics
Aurora, Colorado, United States
RECRUITINGUniverstiy of Colorado Hospital
Aurora, Colorado, United States
RECRUITINGDetermine the Safety of Combination Cirtuvivint with Olaparib
To determine the safety and tolerability of combination Cirtuvivint and Olaparib in BRCA/HRD platinum resistant ovarian cancer as evaluated by CTCAE v5.0 criteria.
Time frame: 6 months
Determine the recommended Phase 2 Dose of Cirtuvivint with Olaparib
To determine the recommended Phase 2 Dose (RP2D) and regimen of the combination therapy
Time frame: 6 months
Evaluate the Cmax (peak plasma concentration) of Cirtuvivint when given in combination with olaparib
To evaluate the Cmax (peak plasma concentration) of Cirtuvivint when given in combination with olaparib
Time frame: 3 years
Evaluate the AUC (Area under the curve for plasma concentration) of Cirtuvivint when given in combination with olaparib
To evaluate the AUC (Area under the curve for plasma concentration) of Cirtuvivint when given in combination with olaparib
Time frame: 3 years
Evaluate the half-life (elimination half-life in plasma) of Cirtuvivint when given in combination with olaparib
To evaluate the half-life (elimination half-life in plasma) of Cirtuvivint when given in combination with olaparib
Time frame: 3 years
Evaluate CL (drug clearance) of Cirtuvivint when given in combination with olaparib
To evaluate CL (drug clearance) of Cirtuvivint when given in combination with olaparib
Time frame: 3 years
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