Olaparib for Metastatic Breast Cancer

Recruiting at 21 trial locations

Overseen By Nadine Tung, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Beth Israel Deaconess Medical Center

Must not be taking: PARP inhibitors, CYP3A inhibitors

Disqualifiers: BRCA1/2 mutation, Brain metastases, MDS/AML, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 24 weeks

114 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is for patients with metastatic breast cancer. * Metastatic means that the cancer has spread beyond the breast. In addition, through genetic testing of the blood or tumor, an altered gene has been found that suggests the tumor may not be able to repair its genetic material (DNA) when it becomes damaged. * This aspect of the cancer may cause it to be more sensitive - that is, more effectively killed by certain types of drugs such as the study agent being evaluated in this trial, Olaparib. * Olaparib is a type of drug known as a PARP inhibitor. Some types of breast cancer and ovarian cancer share some basic features that make them sensitive to similar treatments. Information from those other research studies suggests that this drug may help to treat metastatic breast cancer. * This study will evaluate whether olaparib is effective in breast cancer patients whose tumor has a mutation in one of the other genes that function with BRCA1 and BRCA2 to repair damaged DNA .This mutation may have been inherited from a parent, or may have developed only in the tumor. * This study will also evaluate whether olaparib is effective in breast cancer patients whose tumor has a mutation in BRCA1 or BRCA2 that was acquired by the tumor, but not inherited.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for some drugs. You must stop taking strong or moderate CYP3A inhibitors and inducers before starting the study, with a washout period of 2 to 5 weeks depending on the specific medication. Other medications may be allowed, but it's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug Olaparib for treating metastatic breast cancer?

Olaparib has shown clinical benefits in a phase III trial for patients with BRCA-mutated HER2-negative metastatic breast cancer, improving progression-free survival compared to standard chemotherapy, especially in triple negative breast cancer. ^{1 2 3 4 5}

Is Olaparib safe for humans?

Olaparib (Lynparza) has been studied for safety in various conditions, including breast and ovarian cancer. It generally has a manageable safety profile, meaning that while there are side effects, they are typically not severe and can be managed with medical care. ^{1 4 5 6 7}

How is the drug Olaparib unique in treating metastatic breast cancer?

Olaparib is unique because it is an oral medication specifically designed for patients with BRCA-mutated, HER2-negative metastatic breast cancer, and it works by inhibiting PARP (a protein that helps repair DNA damage in cells), which is particularly effective in cancers with faulty DNA repair mechanisms. This makes it different from standard chemotherapy, as it targets the cancer cells' ability to repair themselves, potentially leading to better outcomes for certain patients. ^{1 2 3 4 5}

Research Team

Nadine Tung, MD

Principal Investigator

Beth Israel Deaconess Medical Center

Eligibility Criteria

This trial is for adults with metastatic breast cancer that has spread beyond the breast and have specific gene mutations (excluding BRCA1/2). Participants must have normal organ/bone marrow function, no more than two prior chemotherapy regimens for metastasis, not be pregnant or breastfeeding, able to take oral medication, and willing to follow study procedures.

Inclusion Criteria

My breast cancer is at stage IV and has been confirmed by tests.

I have a genetic mutation in a DNA repair gene, but not in BRCA1 or BRCA2.

I have not failed more than two chemotherapy treatments for my advanced cancer.

Exclusion Criteria

Pregnant or breast feeding women.

I haven't had cancer in the last 5 years, except for certain types that were fully treated.

I have not had major surgery in the last 2 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Olaparib monotherapy in 21-day cycles, taking the drug twice daily

24 weeks

Tumor measurements every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Treatment Details

Interventions

• Olaparib

Trial Overview The trial tests Olaparib's effectiveness in patients whose tumors are sensitive due to certain genetic mutations. Olaparib is a PARP inhibitor which may help treat cancer by exploiting the tumor's impaired DNA repair ability. The study includes those with inherited or tumor-only mutations.

Participant Groups

Group I: OLAPARIB QD SOMATIC MUTATION - EXPANSION Experimental Treatment 1 Intervention

After the screening procedures confirm eligibility to participate in the research study: * Olaparib: Each study treatment cycle lasts 21 days (3 weeks), taking 2 times per day, 12 hours apart. * Tumor measurements q6 weeks x 24 weeks, then q 12 weeks

Group II: OLAPARIB QD SOMATIC MUTATION Experimental Treatment 1 Intervention

After the screening procedures confirm eligibility to participate in the research study: * Olaparib: Each study treatment cycle lasts 21 days (3 weeks), taking 2 times per day, 12 hours apart. * Tumor measurements q6 weeks x 24 weeks, then q 12 weeks

Group III: OLAPARIB QD GERMLINE MUTATION - EXPANSION Experimental Treatment 1 Intervention

After the screening procedures confirm eligibility to participate in the research study: * Olaparib: Each study treatment cycle lasts 21 days (3 weeks), taking 2 times per day, 12 hours apart. * Tumor measurement q6 weeks x 24 weeks, then q 12 weeks

Group IV: OLAPARIB QD GERMLINE MUTATION Experimental Treatment 1 Intervention

After the screening procedures confirm eligibility to participate in the research study: * Olaparib: Each study treatment cycle lasts 21 days (3 weeks), taking 2 times per day, 12 hours apart. * Tumor measurement q6 weeks x 24 weeks, then q 12 weeks

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

Approved in European Union as Lynparza for:

• Breast cancer
• Ovarian cancer
• Fallopian tube cancer
• Peritoneal cancer
• Pancreatic cancer
• Prostate cancer
• Endometrial cancer

Approved in United States as Lynparza for:

• Ovarian, fallopian tube, and primary peritoneal cancer
• Breast cancer
• Prostate cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

AstraZeneca

Industry 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

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

Findings from Research

Olaparib (Lynparza) is approved for treating adult patients with high-risk early breast cancer that has a germline BRCA mutation, following chemotherapy treatment.

This approval highlights Olaparib's role as an adjuvant therapy, which means it is used after initial treatments to help prevent cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Treatment for High-Risk Early Breast Cancer. Aschenbrenner, DS.[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]

Olaparib is particularly effective for patients with BRCA-mutated ovarian cancer, but it also benefits a subset of patients with BRCA wild-type tumors that have loss-of-function mutations in DNA repair genes, showing similar treatment outcomes.

The study suggests that patients with specific HRR gene mutations, even without BRCA mutations, can be identified as a group that may respond well to olaparib, indicating a potential for broader use of this treatment in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. Hodgson, DR., Dougherty, BA., Lai, Z., 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, a PARP inhibitor, has shown significant clinical benefits in improving progression-free survival for patients with BRCA1 or BRCA2 mutated HER2 negative metastatic breast cancer compared to standard chemotherapy.

The drug has a manageable safety profile, making it a promising treatment option, particularly for triple negative breast cancer, although further research is needed to optimize its use with other therapies and identify suitable biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib for the treatment of breast cancer. Griguolo, G., Dieci, MV., Guarneri, V., et al.[2019]

In a Phase I study involving 28 Japanese patients with advanced solid tumors, olaparib tablets at doses of 200 and 300 mg twice daily were found to be tolerable, with no dose-limiting toxicities reported.

The most common side effects included nausea, decreased appetite, anemia, and constipation, but no confirmed antitumor responses were observed, leading to the selection of 300 mg bid as the recommended dose for future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of the olaparib tablet formulation in Japanese patients with advanced solid tumours. Yonemori, K., Tamura, K., Kodaira, M., et al.[2022]

Olaparib significantly improves overall survival in patients with recurrent platinum-sensitive ovarian cancer, with a hazard ratio of 1.24 based on a meta-analysis of 7 randomized controlled trials involving 2406 patients.

However, the treatment is associated with a higher incidence of adverse events, particularly for grades 3 or higher, indicating that while olaparib is effective, it also carries a risk of significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review of Olaparib in the Treatment of Recurrent Platinum Sensitive Ovarian Cancer. Chen, Q., Li, X., Zhang, Z., et al.[2022]

References

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

New Adjuvant Treatment for High-Risk Early Breast Cancer. [2022]

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

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

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

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. [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

Olaparib for the treatment of breast cancer. [2019]

6. Germany pubmed.ncbi.nlm.nih.gov

Safety and tolerability of the olaparib tablet formulation in Japanese patients with advanced solid tumours. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Systematic Review of Olaparib in the Treatment of Recurrent Platinum Sensitive Ovarian Cancer. [2022]