Testing the Addition of Abemaciclib to Olaparib for Women With Recurrent Ovarian Cancer
A Phase 1/1b Dose Escalation Study of Abemaciclib and Olaparib for Recurrent Platinum-Resistant Ovarian Cancer
3 other identifiers
interventional
42
1 country
27
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jul 2021
Longer than P75 for phase_1
27 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 17, 2020
CompletedFirst Posted
Study publicly available on registry
November 18, 2020
CompletedStudy Start
First participant enrolled
July 2, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
November 1, 2026
May 22, 2026
May 1, 2026
5.3 years
November 17, 2020
May 20, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Recommended phase 2 dose (RP2D)
Safety and tolerability will be measured using Common Terminology Criteria for Adverse Events (CTCAE) version 5. The number of patients experiencing a dose limiting toxicity will be tabulated. The recommended phase 2 dose will be determined by the dose escalation phase using 3+3 design.
28 days (end of cycle 1)
Secondary Outcomes (2)
Overall response rate (ORR)
30 days after completion of study treatment
Duration of response (DoR)
30 days after completion of study treatment
Other Outcomes (1)
Biomarker analysis
30 days after completion of study treatment
Study Arms (1)
Treatment (abemaciclib, olaparib, biospecimen collection)
EXPERIMENTALPatients receive olaparib PO BID on days 1-28 and abemaciclib PO BID on days 8-28 of cycle 1 and days 1-28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and undergo tumor biopsy on study.
Interventions
Given PO
Undergo tumor biopsy
Undergo collection of blood
Given PO
Eligibility Criteria
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
- +22 more criteria
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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (27)
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054, United States
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612, United States
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Kansas Clinical Research Center
Fairway, Kansas, 66205, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210, United States
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064, United States
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri, 64116, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Camille Jackson
Yale University Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 17, 2020
First Posted
November 18, 2020
Study Start
July 2, 2021
Primary Completion (Estimated)
November 1, 2026
Study Completion (Estimated)
November 1, 2026
Last Updated
May 22, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.