Abemaciclib + Olaparib for Recurrent Ovarian Cancer
Palo Alto (17 mi)Overseen byCamille Gunderson
Age: 18+
Sex: Female
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: National Cancer Institute (NCI)
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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.
What safety data is available for the treatment of Abemaciclib and Olaparib in recurrent ovarian cancer?The safety data for Olaparib (Lynparza) in ovarian cancer includes its use as a monotherapy in patients with BRCA mutations, showing common adverse reactions such as anemia, nausea, fatigue, vomiting, diarrhea, and others. Serious conditions like myelodysplastic syndrome and acute myeloid leukemia occurred in 2% of patients. Olaparib has been tested in various trials, including Phase I, II, and III, for its efficacy and safety in different settings of ovarian cancer treatment. However, specific safety data for the combination of Abemaciclib and Olaparib in recurrent ovarian cancer is not detailed in the provided research.13456
Is the drug Abemaciclib + Olaparib promising for treating recurrent ovarian cancer?Yes, the drug combination of Abemaciclib and Olaparib is promising for treating recurrent ovarian cancer. Olaparib has shown significant benefits in improving progression-free survival in patients with ovarian cancer, especially those with BRCA mutations. It is effective as a maintenance therapy and has been approved for use in various settings, demonstrating its potential as a valuable treatment option.12357
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you must stop all current medications. However, there is a required 4-week washout period for agents other than chemotherapy, and a 2-week washout period for strong or moderate CYP3A inhibitors. It's important to discuss your current medications with the trial team to ensure they don't interfere with the study treatment.
What data supports the idea that Abemaciclib + Olaparib for Recurrent Ovarian Cancer is an effective treatment?The available research shows that Olaparib, one of the drugs in the combination, has been effective in treating ovarian cancer, especially in patients with certain genetic mutations. It has shown promise in both relapsed ovarian cancer and as a maintenance therapy after chemotherapy. However, the research provided does not specifically mention the combination of Abemaciclib and Olaparib for recurrent ovarian cancer, so there is no direct data supporting the effectiveness of this specific combination for this condition.13568
Eligibility Criteria
This trial is for women over 18 with recurrent platinum-resistant ovarian cancer, who've had 1-3 prior treatments but no CDK 4/6 inhibitors. They must not be pregnant or breastfeeding, have a good performance status, and agree to contraception. Exclusions include certain medical conditions, recent major surgery, active infections, and known allergies to the drugs tested.Inclusion Criteria
I can care for myself but may not be able to do active work.
My kidney function is good.
My hepatitis C is either cured or undetectable.
My hepatitis B virus load is undetectable with treatment.
My heart function is classified as NYHA 2B or better.
My ovarian cancer has come back and does not respond to platinum-based treatments.
I can take care of myself but might not be able to do heavy physical work.
I have had 1 to 3 treatments for my condition before.
I am a woman aged 18 or older.
Exclusion Criteria
I have been diagnosed with a blood disorder that could be or is turning into leukemia.
I have not had major surgery in the last 2 weeks.
I have an ongoing fungal infection in my body.
I have had a bone marrow or double cord blood transplant.
I am not taking strong or moderate drugs that affect liver enzyme CYP3A.
I currently have a blood clot.
I have heart conditions that are not under control.
I have a serious health condition that is not under control.
I have or might have lung scarring or inflammation.
I am allergic to abemaciclib, olaparib, or their ingredients.
I cannot swallow pills or have stomach issues affecting medication absorption.
Treatment Details
The study tests combining abemaciclib (which blocks enzymes needed for cell growth) with olaparib (a PARP inhibitor preventing tumor DNA repair) in patients whose ovarian cancer has returned after initial treatment success. The goal is to find the safest dose of abemaciclib that works best with olaparib.
1Treatment groups
Experimental Treatment
Group I: Treatment (abemaciclib, olaparib, biospecimen collection)Experimental Treatment4 Interventions
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.
Abemaciclib is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Verzenio for:
- Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
- HR+, HER2- node-positive early breast cancer
🇪🇺 Approved in European Union as Verzenio for:
- HR+, HER2- advanced or metastatic breast cancer
- HR+, HER2- node-positive early breast cancer
Find a clinic near you
Research locations nearbySelect from list below to view details:
University of Kansas Cancer CenterKansas City, KS
Wake Forest University Health SciencesWinston-Salem, NC
University of Kansas Cancer Center at North Kansas City HospitalNorth Kansas City, MO
UM Sylvester Comprehensive Cancer Center at PlantationPlantation, FL
More Trial Locations
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Who is running the clinical trial?
National Cancer Institute (NCI)Lead Sponsor
References
Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer. [2016]Olaparib (Lynparza™; AZD2281) is a potent PARP-1 and PARP-2 inhibitor with biologic activity in ovarian cancer as well as other solid tumors. It has been tested in Phase I and II trials and has single-agent activity in both germline BRCA mutated and sporadic ovarian cancer. Phase III trials assessing the efficacy of olaparib in the maintenance setting following first line and platinum-sensitive recurrence are underway for patients with a germline BRCA mutation, given the inherent molecular compatibility with the drug's mechanism of action.
Olaparib: a review of its use as maintenance therapy in patients with ovarian cancer. [2016]Olaparib (Lynparza™) is a first-in-class, orally-active, small molecule, poly (ADP-ribose) polymerase inhibitor that induces synthetic lethality in homozygous BRCA-deficient cells. In the EU, the capsule formulation of olaparib is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive, relapsed, BRCA-mutated (germline and/or somatic), high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. This approval was based on the results of study 19, a randomized phase II trial in 265 patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer (HGSOC) who had received two or more platinum-based regimens and who had a partial or complete response to their most recent platinum-based regimen. Study 19 met its primary endpoint by demonstrating a significant improvement in progression-free survival in patients receiving olaparib compared with those receiving placebo. Moreover, a preplanned retrospective analysis identified those patients with a BRCA mutation (who comprised one-half of the overall study population) as being the subgroup that derived the greatest clinical benefit from olaparib. Single-agent olaparib was generally well tolerated, with the majority of adverse events being of mild to moderate severity and not requiring interruption of treatment. Fatigue, anaemia and neutropenia were the most frequently reported severe (grade ≥3) adverse events. An as yet unapproved tablet formulation of olaparib that has a lower pill burden than the capsule formulation is currently being investigated in phase III clinical studies.
Safety evaluation of olaparib for treating ovarian cancer. [2015]Olaparib (Lynparza®) is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor that has become the first 'personalized' therapy available for patients with BRCA mutation-positive ovarian cancer (OC). A capsule formulation of the drug has recently received approval for use in this population for platinum-sensitive recurrent disease for maintenance therapy following platinum-based chemotherapy in Europe and as third- or fourth-line platinum-sensitive therapy in the USA.
FDA Approval Summary: Olaparib Monotherapy in Patients with Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated with Three or More Lines of Chemotherapy. [2022]On December 19, 2014, the FDA approved olaparib capsules (Lynparza; AstraZeneca) for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. The BRACAnalysis CDx (Myriad Genetic Laboratories, Inc.) was approved concurrently. An international multicenter, single-arm trial enrolled 137 patients with measurable gBRCAm-associated ovarian cancer treated with three or more prior lines of chemotherapy. Patients received olaparib at a dose of 400 mg by mouth twice daily until disease progression or unacceptable toxicity. The objective response rate (ORR) was 34% with median response duration of 7.9 months in this cohort. The most common adverse reactions (≥20%) in patients treated with olaparib were anemia, nausea, fatigue (including asthenia), vomiting, diarrhea, dysgeusia, dyspepsia, headache, decreased appetite, nasopharyngitis/pharyngitis/upper respiratory infection, cough, arthralgia/musculoskeletal pain, myalgia, back pain, dermatitis/rash, and abdominal pain/discomfort. Myelodysplatic syndrome and/or acute myeloid leukemia occurred in 2% of the patients enrolled on this trial.
Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. [2022]The PARP inhibitor olaparib (Lynparza™) demonstrates antitumor activity in women with relapsed ovarian cancer and a germline BRCA1/2 mutation (gBRCAm). Data from olaparib monotherapy trials were used to explore the treatment effect of olaparib in patients with gBRCAm ovarian cancer who had received multiple lines of prior chemotherapy.
Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. [2020]The poly(ADP-ribose) polymerase inhibitor olaparib (Lynparza™) is approved for maintenance treatment of platinum-sensitive relapsed ovarian cancer. OPINION is a single-arm, open-label, multicenter, Phase IIIb study to assess the efficacy and safety of olaparib tablet maintenance therapy in women with high-grade serous or endometrioid platinum-sensitive relapsed ovarian cancer without a germline BRCA1 or BRCA2 mutation. Eligible patients should have received ≥2 prior lines of platinum-based chemotherapy and be in complete or partial response following their most recent course or have no evidence of disease. Patients will receive olaparib tablets (300 mg twice daily) until disease progression, unacceptable toxicity or another discontinuation criterion. The primary end point is investigator-assessed progression-free survival; secondary end points include progression-free survival according to tumor homologous recombination deficiency status. Clinical trial registration: NCT03402841.
Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer. [2022]Olaparib (Lynparza®) is a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor approved for first-line maintenance treatment in adults with advanced ovarian cancer who are in complete or partial response to first-line, platinum-based chemotherapy. Originally approved as monotherapy, olaparib is also approved to be administered in combination with bevacizumab in patients whose cancer is associated with homologous recombination deficiency (HRD), defined by either a BRCA1/2 mutation and/or genomic instability. In phase III trials, olaparib monotherapy significantly improved progression-free survival (PFS) relative to placebo (SOLO-1), as did olaparib plus bevacizumab relative to placebo plus bevacizumab (PAOLA-1), in patients with advanced ovarian cancer who had responded to platinum-based chemotherapy. In PAOLA-1, improvements in PFS with olaparib plus bevacizumab were not seen in patients with HRD-negative tumours relative to placebo plus bevacizumab. Both olaparib monotherapy and olaparib in combination with bevacizumab had generally manageable tolerability profiles. Olaparib, alone or in combination with bevacizumab, is a useful option for the first-line maintenance treatment of adults with HRD-positive, advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line, platinum-based chemotherapy.
Randomized CLIO/BGOG-ov10 trial of olaparib monotherapy versus physician's choice chemotherapy in relapsed ovarian cancer. [2022]Comparison of olaparib (OLA) monotherapy versus chemotherapy in patients with platinum-sensitive (PSOC) or platinum-resistant ovarian cancer (PROC).