Abemaciclib + Olaparib for Recurrent Ovarian Cancer

Recruiting at 14 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A inhibitors

Disqualifiers: Pregnancy, Cardiac conditions, MDS/AML, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days per cycle

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks to determine the optimal dose and potential side effects of combining two drugs, abemaciclib (a cancer treatment) and olaparib, for treating ovarian cancer that initially responds to platinum-based drugs but later returns. Abemaciclib may inhibit cancer cell growth, while olaparib could prevent these cells from repairing themselves, leading to their death. The trial targets patients whose ovarian cancer recurs within six months after the last platinum-based chemotherapy treatment. Participants should have undergone 1 to 3 prior therapies and have a type of ovarian cancer resistant to platinum-based treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) of at least 21 days for chemotherapy, 28 days for radiotherapy, and 4 weeks for other agents before starting the study treatment. Additionally, a 2-week washout period is needed for certain medications that strongly interact with the trial drugs. Please consult with the trial team to discuss your specific medications.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that olaparib is usually well-tolerated by patients with ovarian cancer. It is already approved for maintenance therapy, helping to prevent the cancer from returning. This approval indicates that its safety is well-understood and acceptable for similar conditions.

Studies have found that abemaciclib can help stop cancer cells from growing by blocking certain enzymes. However, since this is an early phase trial, researchers are still studying the safety and correct dosage of combining abemaciclib with olaparib. As this trial begins, while some information about each drug's safety is known, the combination is new and requires careful monitoring for any side effects. Participants will contribute to understanding how these drugs work together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about abemaciclib and olaparib for recurrent ovarian cancer because they target cancer growth in a unique way. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, olaparib and abemaciclib are more targeted. Olaparib is a PARP inhibitor that interferes with the cancer cell's ability to repair its DNA, while abemaciclib is a CDK4/6 inhibitor that disrupts the cell cycle. By combining these mechanisms, the treatment aims to specifically hinder cancer cell survival and proliferation, offering a potentially more effective and less toxic alternative to standard treatments.

What evidence suggests that this treatment might be an effective treatment for recurrent ovarian cancer?

Research has shown that abemaciclib may stop tumor growth by blocking certain enzymes necessary for tumor development. Olaparib works differently by blocking an enzyme called PARP, which repairs damaged DNA. By inhibiting PARP, olaparib can prevent cancer cells from repairing themselves, leading to their death. Studies indicate that PARP inhibitors like olaparib effectively maintain treatment in ovarian cancer that has returned but still responds to platinum-based drugs. In this trial, participants will receive a combination of abemaciclib and olaparib, which researchers believe will enhance treatment effectiveness for ovarian cancer resistant to platinum-based drugs. Both drugs have shown promise individually, and their combined use could offer a stronger treatment option for patients. ^{1 2 3 6 7}

Who Is on the Research Team?

Camille Jackson

Principal Investigator

Yale University Cancer Center LAO

Are You a Good Fit for This Trial?

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

Creatinine clearance estimated >= 51 mL/min (within 28 days prior to administration of study treatment)

Ability to understand and willingness to sign a written informed consent document

Your bilirubin levels must be within the normal range (as determined by the institution) before starting the study treatment.

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive olaparib orally twice daily on days 1-28 and abemaciclib orally twice daily 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.

28 days per cycle

Regular visits for blood collection and tumor biopsy

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, including overall response rate and duration of response.

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Olaparib

Trial Overview 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.

How Is the Trial Designed?

Group I: Treatment (abemaciclib, olaparib, biospecimen collection) Experimental Treatment 4 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

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Olaparib, approved by the FDA for patients with advanced ovarian cancer carrying BRCA mutations, showed a 34% objective response rate in a trial of 137 patients who had undergone three or more prior chemotherapy treatments, with a median response duration of 7.9 months.

Common side effects included anemia, nausea, and fatigue, with a small risk (2%) of developing myelodysplastic syndrome or acute myeloid leukemia, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Olaparib Monotherapy in Patients with Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated with Three or More Lines of Chemotherapy. Kim, G., Ison, G., McKee, AE., et al.[2022]

Olaparib is an effective treatment for patients with platinum-sensitive, relapsed BRCA-mutated high-grade serous ovarian cancer, showing significant improvement in progression-free survival compared to placebo in a study of 265 patients.

The treatment is generally well tolerated, with most side effects being mild to moderate, although fatigue, anemia, and neutropenia were noted as more severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: a review of its use as maintenance therapy in patients with ovarian cancer. Frampton, JE.[2016]

Olaparib is a powerful inhibitor of PARP-1 and PARP-2, showing effectiveness in treating ovarian cancer, particularly in patients with germline BRCA mutations.

Phase III trials are currently evaluating olaparib's efficacy as a maintenance therapy after initial treatment in patients with BRCA mutations, highlighting its potential role in long-term cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer. Gunderson, CC., Moore, KN.[2016]

Olaparib is an effective oral treatment for patients with BRCA mutation-positive ovarian cancer, approved for maintenance therapy after platinum-based chemotherapy, showing good tolerability with common side effects like nausea, fatigue, and anemia being mild to moderate.

Long-term monitoring is recommended due to a low risk of serious hematological complications, such as anemia and myelodysplastic syndrome, ensuring patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of olaparib for treating ovarian cancer. Lheureux, S., Bowering, V., Karakasis, K., et al.[2015]

Olaparib (OLA) monotherapy showed a similar overall objective response rate (ORR) compared to chemotherapy (CT) in patients with relapsed ovarian cancer, with ORR of 24.3% for OLA and 28.3% for CT, indicating comparable efficacy.

In patients with platinum-resistant ovarian cancer (PROC) who had received more than four prior lines of treatment, OLA demonstrated a higher ORR of 22.9% compared to 0% for CT, suggesting that OLA may be more effective in heavily pretreated cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized CLIO/BGOG-ov10 trial of olaparib monotherapy versus physician's choice chemotherapy in relapsed ovarian cancer. Vanderstichele, A., Loverix, L., Busschaert, P., et al.[2022]

The OPINION study is evaluating the safety and efficacy of olaparib as a maintenance therapy for women with high-grade serous or endometrioid platinum-sensitive relapsed ovarian cancer who do not have BRCA mutations, involving patients who have undergone at least two prior lines of platinum-based chemotherapy.

The primary goal of the study is to assess progression-free survival, which will help determine how effective olaparib is in delaying cancer progression in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. Poveda, AM., Davidson, R., Blakeley, C., et al.[2020]

Olaparib, a PARP inhibitor, showed a 36% objective response rate in women with relapsed ovarian cancer and a germline BRCA1/2 mutation, even after they had undergone multiple lines of chemotherapy, indicating its efficacy in this challenging patient population.

The median duration of response to olaparib was 7.4 months, and the safety profile was consistent across patients who had received three or more lines of prior chemotherapy, with similar rates of serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Matulonis, UA., Penson, RT., Domchek, SM., et al.[2022]

Olaparib is an effective first-line maintenance treatment for adults with advanced ovarian cancer who have responded to platinum-based chemotherapy, significantly improving progression-free survival compared to placebo in phase III trials.

When combined with bevacizumab, olaparib further enhances treatment efficacy in patients with homologous recombination deficiency (HRD), but does not show benefits in HRD-negative tumors, indicating its targeted effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer. Paik, J.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04633239

Testing the Addition of Abemaciclib to Olaparib for Women ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6333551/

New Drug Updates in Solid Tumors: PARP Inhibitors ... Niraparib and olaparib have approval as maintenance therapy for recurrent, platinum-sensitive ovarian cancer. ... Data analysis included 192 patients: 40 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11368096/

Practical Guidance on Abemaciclib in Combination with ... Updated results with 8 years of follow-up data showed that abemaciclib plus AI resulted in an overall 13.1 month increase in OS over AI alone; ...

4. onclive.com onclive.com/view/treatment-in-hr-early-breast-cancer-may-be-best-guided-by-risk-of-recurrence

Treatment in HR+ Early Breast Cancer May be Best Guided ... Abemaciclib may be considered in combination with endocrine therapy in patients with hormone receptor–positive, HER2-negative, high-risk disease.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.01549

Overall Survival With Maintenance Olaparib at a 7-Year ... Results indicate a clinically meaningful, albeit not statistically significant, improvement in OS with maintenance olaparib versus placebo, with ...

6. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/olaparib?pn=1

Clinical Trials Using Olaparib - NCI Testing the Addition of Abemaciclib to Olaparib for Women with Recurrent Ovarian Cancer. Status: Active. Location: 17 locations. Study of Pembrolizumab (MK ...

7. mayo.edu mayo.edu/research/clinical-trials/diseases-conditions/ovarian-cancer

Ovarian Cancer Clinical Trials The purpose of this study is to identify the side effects and best dose of abemaciclib when given together with olaparib in treating patients with ovarian ...