Testing the Addition of Abemaciclib to Olaparib for Women With Recurrent Ovarian Cancer
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|ClinicalTrials.gov Identifier: NCT04633239|
Recruitment Status : Suspended (Other - To review agent toxicities)
First Posted : November 18, 2020
Last Update Posted : July 27, 2022
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Ovarian High Grade Serous Adenocarcinoma Recurrent Platinum-Resistant Ovarian Carcinoma||Drug: Abemaciclib Drug: Olaparib||Phase 1|
I. 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.
I. 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.
I. 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 (ETCTN) Biorepository 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.
After completion of study treatment, patients are followed up at 30 days.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||41 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1/1b Dose Escalation Study of Abemaciclib and Olaparib for Recurrent Platinum-Resistant Ovarian Cancer|
|Actual Study Start Date :||February 12, 2021|
|Estimated Primary Completion Date :||December 1, 2022|
|Estimated Study Completion Date :||December 1, 2022|
Experimental: Treatment (abemaciclib, olaparib)
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.
- Recommended phase 2 dose (RP2D) [ Time Frame: 28 days (end of cycle 1) ]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.
- Overall response rate (ORR) [ Time Frame: 30 days after completion of study treatment ]ORR will be calculated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
- Duration of response (DoR) [ Time Frame: 30 days after completion of study treatment ]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).
- Biomarker analysis [ Time Frame: 30 days after completion of study treatment ]Will measure 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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04633239
|United States, Arizona|
|Mayo Clinic Hospital in Arizona|
|Phoenix, Arizona, United States, 85054|
|United States, Florida|
|Mayo Clinic in Florida|
|Jacksonville, Florida, United States, 32224-9980|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|United States, Minnesota|
|Mayo Clinic in Rochester|
|Rochester, Minnesota, United States, 55905|
|United States, New York|
|NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center|
|New York, New York, United States, 10032|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210|
|United States, Oklahoma|
|University of Oklahoma Health Sciences Center|
|Oklahoma City, Oklahoma, United States, 73104|
|United States, Pennsylvania|
|Thomas Jefferson University Hospital|
|Philadelphia, Pennsylvania, United States, 19107|
|United States, Virginia|
|University of Virginia Cancer Center|
|Charlottesville, Virginia, United States, 22908|
|Principal Investigator:||Camille Gunderson||Yale University Cancer Center LAO|