Recurrent Ovarian High Grade Serous AdenocarcinomaPhase 1NCT04633239
Testing the Addition of Abemaciclib to Olaparib for Women With Recurrent Ovarian Cancer
A Phase 1 study testing Abemaciclib, Biopsy Procedure and Biospecimen Collection in people with Recurrent Ovarian High Grade Serous Adenocarcinoma and Recurrent Platinum-Resistant Ovarian Carcinoma, run by National Cancer Institute (NCI) at 27 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Recurrent Ovarian High Grade Serous Adenocarcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma
- What is being tested?
- Abemaciclib, Biopsy Procedure and Biospecimen Collection
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 27 sitesUnited States
- Study dates
- 2 Jul 2021to 1 Nov 2026
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
- Chemotherapy-induced menopause with > 1 year interval since last menses
- Surgical sterilization (bilateral oophorectomy or hysterectomy)
- The effects of abemaciclib and olaparib on the developing human fetus are unknown. For this reason and because CDK-and PARP-inhibiting agents are known to be teratogenic, women of child-bearing potential and their partners, who are sexually active, must agree to the use of one highly effective form of contraception and their partner must use a male condom prior to study entry, for the duration of study participation, and for 6 months after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- For the dose expansion cohort, patients must have disease amenable to biopsy for correlative studies, specifically at least 1 tumor accessible and safe for biopsy on office exam or tumor that a radiologist deems is safe for biopsy in interventional radiology department based on imaging (dose expansion cohort only). For the dose escalation cohort, patients with evaluable disease are acceptable
- For inclusion in i) the optional genetic research and ii) the optional biomarker research, patients must fulfill the following criteria:
- Provision of informed consent for genetic research prior to collection of sample
- Provision of informed consent for biomarker research prior to collection of sample
- If a patient declines to participate in the optional exploratory genetic research or the optional biomarker research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study
- Patients may not have received prior CDK 4/6 inhibitors. Previous PARP inhibitor use is allowed in front-line treatment but not for recurrent disease
- Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] grade =< 1) from the acute effects of chemotherapy except for residual alopecia or grade 2 peripheral neuropathy prior to randomization. A washout period of at least 21 days is required between last chemotherapy dose and randomization (provided the patient did not receive radiotherapy)
- Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 28 days is required between end of radiotherapy and randomization
- For agents other than chemotherapy, a 4 week washout period is required. Previous bevacizumab use is allowed
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
27 sites in 1 country. Contact the study team or a site near you to ask about taking part.
27 sites in 1 country
United States27 sites, 11 recruiting
- Recruiting
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
Site Public Contact, 434-243-6303, uvacancertrials@hscmail.mcc.virginia.edu
Linda R. Duska
- Active, not recruiting
Northwestern University
Chicago, Illinois, 60611
- Recruiting
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Site Public Contact, 800-293-5066, Jamesline@osumc.edu
John L. Hays
- Active, not recruiting
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146
- Active, not recruiting
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442
- Active, not recruiting
University of Kansas Clinical Research Center
Fairway, Kansas, 66205
- Recruiting
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612
Site Public Contact, 877-827-8839, ucstudy@uci.edu
Sami Dwabe
- Active, not recruiting
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
- Active, not recruiting
University of Kansas Cancer Center
Kansas City, Kansas, 66160
- Active, not recruiting
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154
- Active, not recruiting
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064
- Recruiting
Los Angeles General Medical Center
Los Angeles, California, 90033
Site Public Contact, 323-865-0451, uscnorrisinfo@med.usc.edu
Anastasia Martynova
- Recruiting
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Site Public Contact, 323-865-0451
Anastasia Martynova
- Active, not recruiting
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
- Recruiting
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Site Public Contact, 800-811-8480
Alaina J. Brown
- Terminated
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
- Active, not recruiting
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri, 64116
- Recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Site Public Contact, 405-271-8777, ou-clinical-trials@ouhsc.edu
Lauren E. Dockery
- Recruiting
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
Site Public Contact, 877-827-8839, ucstudy@uci.edu
Sami Dwabe
- Active, not recruiting
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210
- Active, not recruiting
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211
- Recruiting
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Site Public Contact, 215-600-9151, ONCTrialNow@jefferson.edu
Mitchell I. Edelson
- Active, not recruiting
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054
- Active, not recruiting
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324
- Recruiting
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Site Public Contact, 855-776-0015
Andrea E. Wahner Hendrickson
- Active, not recruiting
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205
- Recruiting
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Site Public Contact, 336-713-6771
Janelle Darby
About this study
Official title: A Phase 1/1b Dose Escalation Study of Abemaciclib and Olaparib for Recurrent Platinum-Resistant Ovarian Cancer
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.
Read the detailed description
PRIMARY OBJECTIVE:
- To assess the safety of abemaciclib plus olaparib in patients with platinum-resistant ovarian cancer by determining the maximum tolerated dose and recommended phase 2 dose.
SECONDARY OBJECTIVE:
- To observe and record anti-tumor activity using overall response rate (ORR) and duration of response (DoR) with abemaciclib and olaparib, given in combination, in patients with platinum-resistant ovarian cancer.
EXPLORATORY OBJECTIVES:
- To assess proof of mechanism (RB, phosphoRB, cleaved caspase 3, Ki67, geminin, gamma-H2AX, RAD51 nuclear foci, pNBS multiplex, Myc transcriptional targets ODC1 and LDHA, homologous recombination genes BRCA1, BRCA2, RAD51, serum thymidine kinase), plasma and tumor pharmacokinetics, and subgroups of response (immunohistochemistry [IHC] for Myc, cyclin E; next generation sequencing [NGS]/whole exome sequencing [WES] for DCAF, hormone receptor [HR] repair gene alterations, Myc, and CCNE1; ribonucleic acid sequencing [RNAseq] for Myc and CCNE1).
II. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data, including presentation, diagnosis, staging, summary treatment, and if possible, outcome.
III. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood (for cell-free DNA analysis), and nucleic acids obtained from patients at the Experimental Therapeutics Clinical Trials Network (EET) Biobank at Nationwide Children's Hospital.
OUTLINE: This is a dose-escalation study of abemaciclib.
Patients receive olaparib orally (PO) twice daily (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.
After completion of study treatment, patients are followed up at 30 days.
- Conditions
- Recurrent Ovarian High Grade Serous Adenocarcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma
- Being tested
- Abemaciclib, Biopsy Procedure, Biospecimen Collection, Olaparib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AbemaciclibDrug
Also called LY 2835219, LY-2835219, LY2835219, Verzenio
Given PO
Biopsy ProcedureProcedure or surgery
Also called Biopsy, BIOPSY_TYPE, Bx
Undergo tumor biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo collection of blood
OlaparibDrug
Also called AZD 2281, AZD-2281, AZD2281, KU 0059436
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (abemaciclib, olaparib, biospecimen collection) | Experimental | Patients 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. Receives: Drug: Abemaciclib; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Olaparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 days (end of cycle 1)
Secondary outcomes (2)
Overall response rate (ORR)
ORR will be calculated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Measured: 30 days after completion of study treatment
Duration of response (DoR)
DoR will be calculated using RECIST version 1.1. The duration of overall response is measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
Measured: 30 days after completion of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2020
- Study start2 Jul 2021
- Primary completion1 Nov 2026 (estimated)
- Study completion1 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Ovarian High Grade Serous AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Camille Jackson, Principal investigator, Yale University Cancer Center LAO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04633239
- Sponsor's protocol ID
- NCI-2020-10084
- Other IDs
- NCI-2020-10084, 10422, 10422, UM1CA186689
- Status last verified
- May 2026
- First submitted
- 17 Nov 2020
- Last updated
- 11 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.