Olaparib + Chemotherapy for Advanced Ovarian Cancer

Recruiting at 49 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

162 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination of Olaparib, Carboplatin, and Paclitaxel for advanced ovarian cancer?

Research shows that the combination of Olaparib and Carboplatin is tolerable and provides clinical benefits in certain patients with heavily pretreated ovarian cancer, even if they are resistant to platinum-based treatments. Additionally, Olaparib has shown effectiveness as a maintenance therapy in relapsed ovarian cancer, helping to delay disease progression. ^{1 2 3 4 5}

Is the combination of Olaparib and chemotherapy safe for treating advanced ovarian cancer?

Research shows that Olaparib, when used alone or with chemotherapy, is generally safe for treating ovarian cancer. Common side effects include mild anemia (low red blood cell count), fatigue, vomiting, diarrhea, and nausea, which are usually manageable. ^{3 4 6 7 8}

What makes the drug combination of Olaparib, Carboplatin, and Paclitaxel unique for treating advanced ovarian cancer?

This drug combination is unique because it combines Olaparib, a PARP inhibitor that targets cancer cells with specific genetic mutations, with Carboplatin and Paclitaxel, which are chemotherapy drugs that work by damaging the DNA of cancer cells. This combination aims to enhance the effectiveness of treatment by using different mechanisms to control the disease. ^{1 3 5 9 10}

What is the purpose of this trial?

To compare the efficacy of olaparib in combination with paclitaxel and carboplatin (AUC4) when compared with carboplatin (AUC6) and paclitaxel alone in patients with advanced ovarian cancer.

Research Team

Amit Oza, MD

Principal Investigator

Princess Margaret Hospital, Canada

Jane Robertson, BSc, MBCHB, MD

Principal Investigator

AstraZeneca

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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 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 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]

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]

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]

References

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

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

2. United States 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. [2023]

3. 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]

4. 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]

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

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

6. United States 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. [2022]

7. New Zealand 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. [2020]

8. England pubmed.ncbi.nlm.nih.gov

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

9. France pubmed.ncbi.nlm.nih.gov

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

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

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