Abemaciclib + Olaparib for Recurrent Ovarian Cancer

Recruiting in Palo Alto (17 mi)

+22 other locations

Overseen by Camille Jackson

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A inhibitors

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

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.

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.

What data supports the effectiveness of the drug Abemaciclib + Olaparib for recurrent ovarian cancer?

Research shows that Olaparib, one of the drugs in the treatment, is effective in treating ovarian cancer, especially in patients with certain genetic mutations (BRCA1/2). It has shown promise in both relapsed ovarian cancer and as a maintenance therapy after chemotherapy. ^{1 2 3 4 5}

What safety information is available for Olaparib in treating ovarian cancer?

Olaparib (Lynparza) has been tested in various studies for ovarian cancer, showing common side effects like nausea, fatigue, vomiting, and anemia. Serious conditions like myelodysplastic syndrome (a blood disorder) and acute myeloid leukemia (a type of blood cancer) occurred in about 2% of patients. ^{1 2 3 5 6}

What makes the drug combination of Abemaciclib and Olaparib unique for treating recurrent ovarian cancer?

The combination of Abemaciclib and Olaparib is unique because it combines a CDK4/6 inhibitor (Abemaciclib) with a PARP inhibitor (Olaparib), potentially offering a novel approach by targeting different pathways involved in cancer cell growth and DNA repair, which may enhance treatment effectiveness for recurrent ovarian cancer compared to using either drug alone. ^{1 3 5 7 8}

Research Team

Camille Jackson

Principal Investigator

Yale University Cancer Center LAO

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

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.

Trial Timeline

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

Treatment Details

Interventions

• Abemaciclib (CDK4/6 Inhibitor)
• Olaparib (PARP Inhibitor)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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 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]

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, 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 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]

References

1. England 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of olaparib for treating ovarian cancer. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

Randomized CLIO/BGOG-ov10 trial of olaparib monotherapy versus physician's choice chemotherapy in relapsed ovarian cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

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

6. United States 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. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

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

8. France pubmed.ncbi.nlm.nih.gov

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