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

NCT06856499 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 24-1749.ccR01CA288651-01NCI-2024-09126
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Endometrioid Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  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

  6 months

Secondary Outcomes (4)

• Evaluate the Cmax (peak plasma concentration) of Cirtuvivint when given in combination with olaparib

  3 years

• Evaluate the AUC (Area under the curve for plasma concentration) of Cirtuvivint when given in combination with olaparib

  3 years

• Evaluate the half-life (elimination half-life in plasma) of Cirtuvivint when given in combination with olaparib

  3 years

• Evaluate CL (drug clearance) of Cirtuvivint when given in combination with olaparib

  3 years

Study Arms (2)

Dose Regimen 1

EXPERIMENTAL

Patients on Dose Regimen 1 will take 300mg PO BID olaparib in combination with 80mg PO cirtuvivint for 5 days on and 2 days off.

Drug: Cirtuvivint; Drug: Olaparib

Dose Regimen 2

EXPERIMENTAL

Patients on Dose Regimen 2 will take 300 mg PO BID olaparib in combination with 120 mg PO cirtuvivint for 2 days on and 5 days off

Drug: Cirtuvivint; Drug: Olaparib

Interventions

Olaparib DRUG

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.

Also known as: Lynparza

Dose Regimen 1; Dose Regimen 2

Cirtuvivint DRUG

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.

Dose Regimen 1; Dose Regimen 2

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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
• 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)

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

CU Medicine Clinics

Aurora, Colorado, 80045, United States

RECRUITING

Universtiy of Colorado Hospital

Aurora, Colorado, 80045, United States

RECRUITING

MeSH Terms

Conditions

Fallopian Tube Neoplasms

Interventions

olaparib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Bradley Corr

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kailey Palmen, BA

CONTACT

303-724-2435; kailey.palmen@cuanschutz.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2025
• First Posted: March 4, 2025
• Study Start: December 8, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2029
• Last Updated: June 4, 2026

Record last verified: 2026-01

Locations

US (2)