Testing the Addition of Abemaciclib to Olaparib for Women With Recurrent Ovarian Cancer

Recruiting now · Phase 1

Conditions studied: Recurrent Ovarian High Grade Serous Adenocarcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma

In brief

This phase I/Ib trial identifies the side effects and best dose of abemaciclib when given together with olaparib in treating patients with ovarian cancer that responds at first to treatment with drugs that contain the metal platinum but then comes back within a certain period (recurrent platinum-resistant). Abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep tumor cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Adding abemaciclib to olaparib may work better to treat recurrent platinum-resistant ovarian cancer.

Key facts

Study ID

NCT04633239

Run by

National Cancer Institute (NCI)

People needed

42

Starts

2021-07-02

Expected to finish

2026-11-01

Last updated by the study team

2026-07-09

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

• Patients must have histologically confirmed recurrent platinum-resistant epithelial ovarian carcinoma (EOC) of any histology, as defined by progression within 6 months of the last dose of platinum-based chemotherapy. Both primary platinum resistant and acquired platinum resistant patients are allowed
• High-grade serous histology is required (for the dose expansion cohort only) (data on BRCA (e.g. germline BRCA, Somatic BRCA, Neither, Unknown) and homologous recombination deficiency (HRD)/Loss of Heterozygosity (LOH) (e.g. HRD > 42/LOH >16%, HRD score < 42/LOH < 16%, Unknown) is not required for study but will be collected if available
• Patients must have received 1-3 prior systemic therapies
• Women age >= 18 years. Because no dosing or adverse event data are currently available on the use of abemaciclib in combination with olaparib in patients <18 years of age, children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Hemoglobin >= 10 g/dL (within 28 days prior to administration of study treatment)
• Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion
• Absolute neutrophil count >= 1,500/mcL (within 28 days prior to administration of study treatment)
• Platelets >= 100,000/mcL (within 28 days prior to administration of study treatment)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to administration of study treatment)
• Patients with Gilbert's syndrome with a total bilirubin =< 2.0 times ULN and direct bilirubin within normal limits are permitted
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x institutional ULN, unless liver metastases are present in which case they must be =< 5 x ULN (within 28 days prior to administration of study treatment)
• Patients must have creatinine clearance estimated of >= 51 mL/min using the Cockcroft-Gault equation or based on a 24-hour urine test (within 28 days prior to administration of study treatment)
• Glomerular filtration rate (GFR) >= 60 mL/min/1.73 m\^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m\^2 (within 28 days prior to administration of study treatment). Estimated GFR calculated using Cockcroft-Gault equation
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
• Patients with treated brain metastases are eligible if patient is stable for at least 4 weeks status post (s/p) radiation therapy and off corticosteroids, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT] scan) during the screening period
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
• Postmenopausal or evidence of non-childbearing status, a negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1. Postmenopausal is defined as:
• Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
• Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the postmenopausal range for women under 50
• Radiation-induced oophorectomy with last menses > 1 year ago

You may not qualify if…

• Patients who are receiving any other investigational agents
• History of allergic reaction or hypersensitivity attributed to compounds of similar chemical or biologic composition to abemaciclib, olaparib or any of the excipients of these products
• Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study treatment is 2 weeks. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• Patients with psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because abemaciclib is a CDK-inhibiting agent and olaparib is a PARP inhibiting agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with abemaciclib and olaparib, breastfeeding should be discontinued if the mother is treated with abemaciclib and olaparib
• Other malignancy unless curatively treated with no evidence of disease for >= 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), stage 1, grade 1 endometrial carcinoma
• Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT [QTcF] prolongation > 500 ms, electrolyte disturbances, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest, etc.), or patients with congenital long QT syndrome
• Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML)
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection that, in the judgment of the investigator, would preclude participation in this study. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance < 30 ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea)
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
• Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
• Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
• Patients with an active systemic fungal infection
• Patients with suspected or history of interstitial lung disease (ILD)/pneumonitis
• Patients with active thromboembolism. Active thromboembolism is defined as a diagnosis of a thromboembolic within the last 6 months or continued evidence of thromboembolism on imaging despite stable anti-coagulation for 6 months. Patients with a history of thromboembolism > 6 months ago on anti-coagulation as continued prevention are eligible

Where it is running

• Los Angeles General Medical Center — Los Angeles, California, United States (enrolling)
• Mayo Clinic in Rochester — Rochester, Minnesota, United States (enrolling)
• University of Kansas Clinical Research Center — Fairway, Kansas, United States (enrolling)
• USC / Norris Comprehensive Cancer Center — Los Angeles, California, United States (enrolling)
• UC Irvine Health/Chao Family Comprehensive Cancer Center — Orange, California, United States (enrolling)
• UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care — Irvine, California, United States (enrolling)
• Wake Forest University Health Sciences — Winston-Salem, North Carolina, United States (enrolling)
• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States (enrolling)
• University of Oklahoma Health Sciences Center — Oklahoma City, Oklahoma, United States (enrolling)
• Thomas Jefferson University Hospital — Philadelphia, Pennsylvania, United States (enrolling)
• Vanderbilt University/Ingram Cancer Center — Nashville, Tennessee, United States (enrolling)
• University of Virginia Cancer Center — Charlottesville, Virginia, United States (enrolling)
• University of Kansas Cancer Center - Lee's Summit — Lee's Summit, Missouri, United States
• University of Kansas Cancer Center at North Kansas City Hospital — North Kansas City, Missouri, United States
• NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center — New York, New York, United States
• University of Kansas Cancer Center-Overland Park — Overland Park, Kansas, United States
• UM Sylvester Comprehensive Cancer Center at Coral Gables — Coral Gables, Florida, United States
• UM Sylvester Comprehensive Cancer Center at Deerfield Beach — Deerfield Beach, Florida, United States
• Mayo Clinic in Florida — Jacksonville, Florida, United States
• University of Miami Miller School of Medicine-Sylvester Cancer Center — Miami, Florida, United States
• UM Sylvester Comprehensive Cancer Center at Plantation — Plantation, Florida, United States
• Northwestern University — Chicago, Illinois, United States
• University of Kansas Cancer Center — Kansas City, Kansas, United States
• Mayo Clinic Hospital in Arizona — Phoenix, Arizona, United States
• University of Kansas Hospital-Indian Creek Campus — Overland Park, Kansas, United States

Full record on ClinicalTrials.gov

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