RecruitingPhase 1

Cirtuvivint/Olaparib in Breast Cancer Susceptibility Gene/Homologous Recombination Deficiency Platinum Resistant Ovarian Cancer

Phase I Evaluation of Combination CLK/DYRK (Cirtuvivint) Inhibition With PARP Inhibition (Olaparib) in BRCA/HRD Platinum Resistant Ovarian Cancer

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
Female only
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Time periods mentioned: 28 days
  • Procedures mentioned: Blood draws, Physical exams

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "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."
  • "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."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests how safe cirtuvivint and olaparib are when taken together and finds a recommended dose. It is for adult women with certain ovarian, fallopian tube, or abdominal lining cancers that grew within 6 months after platinum chemotherapy and have certain gene or DNA repair changes.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be a woman age 18 or older who can do self-care and is up and about at least half of waking hours.
  • Have confirmed high-grade serous or endometrioid cancer of the ovary, fallopian tube, or peritoneum (the lining inside the belly).
  • Have cancer that can be measured on scans and grew less than 6 months after the last dose of platinum chemotherapy.
  • Have had at least one platinum chemotherapy treatment plan and no more than 3 lines of whole-body cancer treatment. Some treatments count together as one line.
  • Have had both BRCA gene testing and HRD testing, with at least one positive result. These tests look for changes in how cells repair DNA.
  • Have already taken a PARP inhibitor, a type of cancer drug, as treatment or to help keep cancer under control.
  • Have blood counts, liver tests, and kidney tests that meet the study's limits, with no blood transfusion in the past 28 days.
  • Give signed consent and be willing to follow study visits and procedures. People who need help making decisions may qualify with a legal representative or family member available.

Who can't join

  • Have an ovarian tumor type not allowed in this study, or cancer that grew during platinum chemotherapy or within 4 weeks of receiving it.
  • Had whole-body chemotherapy or radiation within 3 weeks before study treatment, except radiation to ease symptoms; or surgery within 2 weeks. You must also have recovered from major surgery.
  • Have myelodysplastic syndrome or acute myeloid leukemia (bone marrow or blood cancers), or signs of either.
  • Have a serious uncontrolled illness or infection, including an infection needing antibiotics through a vein within 2 weeks before treatment.
  • Have serious heart disease, a heart attack or stroke within 6 months, or moderate to severe cirrhosis (liver scarring).
  • Still have moderate or worse side effects from earlier cancer treatment, except hair loss or nerve damage affecting feeling; or have untreated or symptom-causing cancer spread to the brain or spinal cord.
  • Cannot swallow the study pills, have a gut problem that blocks their absorption, or have a known allergy to the study drugs or their ingredients.
  • Cannot follow study visits and procedures, or the study doctor finds you medically unfit for the trial.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

Inclusion Criteria: 1. Provision to sign and date the consent form. 2. Stated willingness to comply with all study procedures and be available for the duration of the study. 3. Woman aged ≥18 years of age 4. Patients must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 1 or 2 5. Patients must have a confirmed diagnosis of high-grade serous or endometrioid epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer 6. Patients must have platinum-resistant disease defined as radiographic progression less than 6 months from last dose of most recent platinum therapy 7. Patients must have measurable disease by defined RECIST 1.1 criteria 8. 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 9. 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. 10. Patients must have received a prior PARP inhibitor as either treatment or maintenance therapy 11. 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 12. 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. 13. 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. Exclusion Criteria: 1. Patients with clear cell, mucinous, sarcomatous, low grade/borderline, germ cell, or sex-cord stromal type ovarian tumor 2. Patients with platinum refractory disease as defined by those who have progressed during or within 4 weeks of receiving platinum-based therapy 3. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment 4. Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of myelodysplastic syndrome/acute myeloid leukemia. 5. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to: * Uncontrolled major seizure disorder * Unstable spinal cord compression * Any psychiatric disorder that prohibits obtaining informed consent. * Any other concurrent infectious disease requiring IV antibiotics within 2 weeks prior to the first dose of therapy 6. Patients with clinically significant cardiac disease including, but not limited to, any of the following * Myocardial infarction ≤ 6 months prior to first dose * Uncontrolled ventricular arrhythmia, recent (within 3 months) * Superior vena cava syndrome * Unstable angina pectoris * Uncontrolled congestive heart failure (New York Heart Association \> class II) * Uncontrolled ≥ Grade 3 hypertension (per CTCAE) * Uncontrolled cardiac arrhythmias 7. Patients with a history of hemorrhagic or ischemic stroke within 6 months prior to enrollment 8. Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C) 9. Persistent toxicities (\>/= Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia or peripheral sensory neuropathy 10. Patients with duodenal stent or other GI disorder/defect that would interfere with absorption of oral medication o Includes patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication 11. Patients with known untreated or symptomatic central nervous system (CNS) metastases 12. Prior known hypersensitivity reaction to study drugs and/or any of their excipients 13. Minor or major surgical procedure within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery. 14. Inability to comply with study and follow-up procedures 15. Patients deemed otherwise clinically unfit for clinical trial per investigators discretion.

Study sites (2)

CO