Phase I Evaluation of Combination CLK/DYRK (Cirtuvivint) Inhibition With PARP Inhibition (Olaparib) in BRCA/HRD Platinum Resistant Ovarian Cancer
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 must have a confirmed diagnosis of high-grade serous or endometrioid epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer
• Patients must have platinum-resistant disease defined as radiographic progression less than 6 months from last dose of most recent platinum therapy
• Patients must have measurable disease by defined RECIST 1.1 criteria
• Prior anticancer therapy:
‣ Patients must have received at least one prior platinum-based chemotherapy regimen
⁃ Patients may not have received more than 3 prior lines of systemic therapy
⁃ Neoadjuvant +/- adjuvant therapies are considered 1 line of therapy
⁃ Maintenance therapy (eg, Bevacizumab, PARP inhibitors) will be considered part of preceding line of therapy (ie, not counted independently)
⁃ Therapy changed due to toxicity in the absence of progression will be considered part of the same line (ie, not counted independently)
⁃ Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance
⁃ Prior radiation is allowed and is not considered a line of treatment
• Patients must have had testing for BRCA mutation (tumor or germline) and tumor HRD testing, and have been positive for one and/or the other.
⁃ Patients must have received a prior PARP inhibitor as either treatment or maintenance therapy
⁃ Patients must have adequate hematologic, liver, and kidney function as defined as:
∙ Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1500/µL)
‣ Platelet count ≥ 100 x 109/L (100,000 µL)
‣ Hemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days
‣ Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
‣ Patients must have creatinine clearance estimated of ≥51 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test
‣ Aspartate aminotransferase (AST)(Serum Glutamic Oxaloacetic Transaminase (SGOT)) and alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x ULN unless liver metastases are present in which case they must be ≤ 5x ULN
‣ Serum bilirubin ≤ 1.5 x ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin \< 3.0 x ULN)
‣ Serum albumin ≥ 2 g/dL
⁃ Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
⁃ Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible.