Olaparib + Chemotherapy for Advanced Ovarian Cancer

Not currently recruiting at 59 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must not be taking: Systemic anticancer chemotherapy

Disqualifiers: Hypersensitivity, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 21

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding the drug olaparib to standard chemotherapy can more effectively combat advanced ovarian cancer. Researchers will compare two treatment groups: one receiving olaparib (also known as Lynparza) with paclitaxel and carboplatin, and another receiving only paclitaxel and carboplatin. Women diagnosed with serous ovarian cancer who have responded well to previous platinum treatments and have measurable tumors may be suitable candidates. The study seeks to identify a more effective treatment option for those battling this type of cancer. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop taking my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications, but you cannot be on any systemic anticancer chemotherapy or radiotherapy within two weeks before starting the study treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that olaparib is generally well-tolerated by patients with advanced ovarian cancer. In earlier studies, participants taking olaparib experienced some side effects, but these were usually manageable. Common side effects included nausea, tiredness, and low blood cell counts, but most patients did not need to stop treatment because of these issues.

The FDA has already approved olaparib for treating certain types of ovarian cancer, indicating it has been tested in many patients and found to be safe enough for use.

The chemotherapy drugs carboplatin and paclitaxel are standard treatments for ovarian cancer and have been used for many years. Their side effects, such as hair loss, nausea, and risk of infections, are well-known and often manageable.

Overall, the treatments in this trial have been studied before, and their safety is well-documented. Patients considering joining the trial should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment involving Olaparib combined with chemotherapy for advanced ovarian cancer because Olaparib offers a targeted approach that differs from standard chemotherapy alone. Olaparib is a PARP inhibitor, which means it works by blocking an enzyme cancer cells need to repair their DNA, leading to cancer cell death while sparing normal cells. This targeted action can enhance the effectiveness of traditional chemotherapy drugs like carboplatin and paclitaxel, potentially improving outcomes for patients. Additionally, Olaparib is taken orally, which can be more convenient compared to intravenous chemotherapy. This combination could provide a more effective and patient-friendly treatment option for those with advanced ovarian cancer.

What evidence suggests that this trial's treatments could be effective for advanced ovarian cancer?

Research has shown that olaparib, one of the treatments tested in this trial for advanced ovarian cancer, appears promising. In one study, 61% of patients taking olaparib were alive, and their cancer had not worsened after an average of 3.4 years. Another study found that olaparib significantly increased the time patients lived without their cancer worsening to over four and a half years, compared to just 13.8 months with a placebo. Additionally, when used as ongoing treatment, olaparib helped prevent cancer growth. In this trial, participants will receive either olaparib or a chemotherapy regimen of paclitaxel and carboplatin. These findings suggest that olaparib could effectively treat advanced ovarian cancer when combined with chemotherapy. ^{3 6 7 8 9}

Who Is on the Research Team?

Amit Oza, MD

Principal Investigator

Princess Margaret Hospital, Canada

Jane Robertson, BSc, MBCHB, MD

Principal Investigator

AstraZeneca

Are You a Good Fit for This Trial?

This trial is for patients with advanced ovarian cancer who have had no more than three prior platinum treatments and were progression-free for at least six months after the last one. They must have at least one measurable lesion and be diagnosed with serous ovarian cancer. Those with recent chemotherapy, radiotherapy, or hypersensitivity to related medications cannot participate.

Inclusion Criteria

I have been diagnosed with serous ovarian cancer.

You have a visible and measurable lesion that can be monitored over time.

I've had up to 3 platinum treatments and was stable for 6+ months after.

Exclusion Criteria

I haven't had chemotherapy or radiotherapy (except for pain relief) in the last two weeks.

I am allergic to the medications given before paclitaxel/carboplatin treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olaparib in combination with paclitaxel and carboplatin or paclitaxel and carboplatin alone

18 weeks

Radiologic scans at weeks 9 and 18

Follow-up

Participants are monitored for progression-free survival and overall survival

20 months

Every 12 weeks

Long-term follow-up

Participants are contacted every 12 weeks to assess survival status

50 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Olaparib
• Paclitaxel

Trial Overview The study compares the effectiveness of Olaparib combined with Carboplatin and Paclitaxel versus just Carboplatin and Paclitaxel in treating advanced ovarian cancer. The goal is to see if adding Olaparib improves patient outcomes.

How Is the Trial Designed?

Group I: 1 Experimental Treatment 3 Interventions

Olaparib is available as a film-coated tablet containing 150 mg or 100 mg of olaparib. Subjects will be administered study treatment orally at a dose recommended by Investigator. Full dose: 300 mg twice daily (bid) or Reduced doses: 200 mg twice daily (bid) or 100 mg twice daily (bid). The planned dose of 300 mg bid will be made up of two x 150 mg tablets twice daily, with 100 mg tablets used to manage dose reductions.

Group II: 2 Active Control 2 Interventions

paclitaxel iv and carboplatin iv

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

The combination of olaparib and carboplatin was found to be safe and effective in treating breast and ovarian cancer in patients with germline BRCA1 or BRCA2 mutations, with 50% of patients showing a partial response and one patient achieving a complete response.

Proteomic analysis indicated that high levels of FOXO3a expression before treatment may predict a better response to the therapy, suggesting a potential biomarker for future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses. Lee, JM., Hays, JL., Annunziata, CM., 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]

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 significantly improves progression-free survival (PFS) in patients with platinum-sensitive BRCA-mutated ovarian cancer, with a hazard ratio of 0.31, indicating a strong benefit compared to placebo or chemotherapy.

The treatment also shows a slight improvement in overall survival (OS) with a hazard ratio of 0.75, while maintaining a manageable safety profile with mostly mild adverse effects like anemia and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of olaparib maintenance therapy in platinum-sensitive ovarian cancer patients with BRCA mutations: a meta-analysis on randomized controlled trials. Ma, J., Deng, H., Li, J., et al.[2020]

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]

In a study of 120 ovarian cancer patients, the combination of olaparib with paclitaxel and carboplatin significantly improved the objective remission rate and disease control rate compared to the standard treatment with paclitaxel and carboplatin alone.

The addition of olaparib also resulted in lower levels of tumor markers and a reduced rate of tumor metastasis after one year, all without increasing the incidence of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib and paclitaxel in combination with carboplatin in treatment of ovarian cancer: influence on disease control. Zhang, H., Zhang, Y.[2022]

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 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]

The combination of olaparib and carboplatin is tolerable and shows clinical benefit in patients with BRCA wild-type high-grade serous ovarian carcinoma, with a clinical benefit rate of 64% in heavily pretreated patients.

The maximum tolerated dose was established at olaparib 400 mg twice daily with carboplatin AUC4, although significant side effects like neutropenia and thrombocytopenia were observed, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/Ib study of olaparib and carboplatin in heavily pretreated recurrent high-grade serous ovarian cancer at low genetic risk. Lampert, EJ., Hays, JL., Kohn, EC., et al.[2023]

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]

Citations

1. lynparza.com lynparza.com/ovarian-cancer/results/advanced-ovarian-cancer.html

Results of LYNPARZA: advanced ovarian cancer 61% of patients (158 out of 260) taking LYNPARZA were alive and did not see their cancer grow or return at a median follow-up of 3.4 years (41 months) compared ...

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

Overall Survival With Maintenance Olaparib at a 7-Year ... Maintenance therapy with the poly(ADP-ribose) polymerase inhibitor olaparib provided a sustained progression-free survival benefit in patients with newly ...

3. merck.com merck.com/news/lynparza-olaparib-improved-median-progression-free-survival-to-over-four-and-a-half-years-compared-to-13-8-months-with-placebo-for-patients-with-brca-mutated-advanced-ovarian-cancer/

LYNPARZA® (olaparib) Improved Median Progression ... LYNPARZA improved progression-free survival to over four and half years versus 13.8 months with placebo following response to first-line platinum-based ...

4. merck.com merck.com/news/lynparza-olaparib-in-combination-with-bevacizumab-and-as-monotherapy-demonstrates-clinically-meaningful-long-term-survival-in-certain-patients-with-first-line-advanced-ovarian-cancer-in-expl/

LYNPARZA® (olaparib) in Combination With Bevacizumab ... Final overall survival (OS), a key secondary endpoint, in those who received LYNPARZAplus bevacizumab was 56.5 months versus 51.6 months with ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4992984/

Efficacy and safety of olaparib monotherapy in germline ... With olaparib monotherapy, objective tumor response rates in Study 42 were 26% for all patients with gBRCA1/2m cancers, and 31% for patients with gBRCA1/2m ...

6. lynparzahcp.com lynparzahcp.com/ovarian-cancer/home.html

LYNPARZA PARP Inhibitor for Advanced Ovarian Cancer LYNPARZA® (olaparib) is a PARPi approved for first-line maintenance in BRCAm and HRD-positive advanced ovarian cancer.

7. lynparzahcp.com lynparzahcp.com/ovarian-cancer/safety-tolerability/solo-1.html

Safety & Tolerability in the SOLO-1 Trial Learn about the safety profile and tolerability of LYNPARZA® (olaparib) as well as the potential adverse reactions found in the SOLO-1 ...

8. lynparza.com lynparza.com/ovarian-cancer/home.html

Advanced or Recurrent Ovarian Cancer Without maintenance therapy, advanced ovarian cancer may return in about 70% of women within 3 years after their first treatment course, even in those who have ...

9. tandfonline.com tandfonline.com/doi/full/10.1080/01443615.2022.2151883

Efficacy and safety of olaparib in advanced ovarian cancer Olaparib maintenance therapy for advanced OC has been shown to reduce tumour size, prolong progression-free survival (PFS), and improve objective response ...