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.
Provision to sign and date the consent form.
Stated willingness to comply with all study procedures and be available for the duration of the study.
Woman aged ≥18 years of age
Patients must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 1 or 2
Patients with clear cell, mucinous, sarcomatous, low grade/borderline, germ cell, or sex-cord stromal type ovarian tumor
Patients with platinum refractory disease as defined by those who have progressed during or within 4 weeks of receiving platinum-based therapy
Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of myelodysplastic syndrome/acute myeloid leukemia.
Parallel
Cirtuvivint
DrugCirtuvivint (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.
Olaparib
DrugNCI 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.
Determine 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.
Determine the recommended Phase 2 Dose of Cirtuvivint with Olaparib
To determine the recommended Phase 2 Dose (RP2D) and regimen of the combination therapy
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
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
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
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
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University of Colorado, Denver
Lead sponsor
National Institutes of Health (NIH)
Collaborator
National Cancer Institute (NCI)
Collaborator
