Olaparib for Bladder Cancer

Recruiting at 17 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A inhibitors/inducers

Disqualifiers: Brain metastases, Liver disease, Stroke, 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: 2

Duration: 28 days per cycle, ongoing

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial studies how well olaparib works in patients with advanced bladder and other genitourinary cancers that have DNA-repair defects. Olaparib is a drug that stops cancer cells from fixing their damaged DNA, which can help to stop the cancer from growing. The trial targets patients whose cancers have spread and are not responsive to standard treatments.

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

The trial requires a washout period (time without taking certain medications) of 2 weeks for chemotherapy and 4 weeks for monoclonal antibodies before starting the study. Additionally, if you are taking strong or moderate CYP3A inhibitors or inducers, you will need a washout period of 5 half-lives or 3 weeks, whichever is shorter. Please consult with your doctor about your specific medications.

Is Olaparib generally safe for humans?

Olaparib, also known as Lynparza, has been used in various cancer treatments and is generally considered to have a manageable safety profile. Common side effects include nausea, fatigue, and anemia, while more serious effects like myelodysplastic syndrome (a blood disorder) and acute myeloid leukemia (a type of blood cancer) are rare. ^{1 2 3 4 5}

How is the drug Olaparib unique in treating bladder cancer?

Olaparib is unique because it is a poly (ADP-ribose) polymerase (PARP) inhibitor, which works by targeting cancer cells with BRCA mutations, a mechanism not commonly used in bladder cancer treatments. It is an oral medication, which can be more convenient compared to traditional intravenous chemotherapy. ^{2 4 6 7 8}

What data supports the effectiveness of the drug Olaparib for bladder cancer?

Olaparib, a drug originally used for ovarian cancer, has shown promise in treating tumors with specific genetic mutations (BRCA1/BRCA2). While direct evidence for bladder cancer is limited, a study suggests that Olaparib may work well in bladder cancer cells, especially when combined with another drug called Metformin. ^{2 4 7 9 10}

Who Is on the Research Team?

Andrea B Apolo

Principal Investigator

National Cancer Institute LAO

Are You a Good Fit for This Trial?

Adults with advanced bladder cancer or genitourinary tumors that have DNA-repair defects and can't be cured by standard treatments. Participants must have specific genetic changes, provide a tumor sample, not be pregnant or fathering children, and meet certain health criteria like good organ function and blood counts.

Inclusion Criteria

I can understand and am willing to sign the consent form, or I have someone legally authorized to do so on my behalf.

My genetic test shows benign or uncertain results.

Women of child-bearing potential and their partners should agree to use two (2) highly effective forms of contraception throughout study participation and for at least one (1) month after the last dose of olaparib. Male study participants should avoid fathering a child or donating sperm during the study and for three (3) months after the last dose of olaparib

Exclusion Criteria

You have had allergic reactions to drugs similar to olaparib.

I have been diagnosed with myelodysplastic syndrome or acute myeloid leukemia.

I have lasting side effects from cancer treatment, except for hair loss.

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 of each cycle, with cycles repeating every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle, ongoing

Regular visits for blood sample collection, imaging, and optional biopsies

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 4 weeks, every 2 months for 1 year, then every 3 months thereafter.

Up to 5 years

Follow-up visits every 2 months for 1 year, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib

Trial Overview The trial is testing Olaparib, a PARP inhibitor designed to prevent cancer cells from repairing their DNA, potentially stopping their growth. It's for patients whose cancer has spread and involves collecting biospecimens to study the treatment's effectiveness.

How Is the Trial Designed?

Group I: Cohort II (biospecimen collection) Experimental Treatment 7 Interventions

Patients that do not have cancer-associated DNA-repair gene mutations undergo blood sample collection at baseline. Additionally, patients undergo CT, MRI, PET/CT, or bone scan and optional tumor biopsy and bone marrow biopsy on study.

Group II: Cohort I (olaparib) Experimental Treatment 8 Interventions

Patients that have cancer-associated DNA-repair gene mutations receive olaparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT, MRI, PET/CT, or bone scan and optional tumor biopsy and bone marrow biopsy on study.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

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 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]

The combination of olaparib, a PARP inhibitor, and metformin significantly enhances the inhibition of bladder cancer cell growth, migration, and invasion compared to using either drug alone.

Metformin appears to boost the antitumor effects of olaparib by downregulating proteins in the STAT3/C-MYC signaling pathway, suggesting a potential new strategy for bladder cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin Can Enhance the Inhibitory Effect of Olaparib in Bladder Cancer Cells. Chi, BJ., Sun, Y., Quan, LL., et al.[2022]

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 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]

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 oral medication that inhibits poly (ADP-ribose) polymerase and is primarily developed for treating BRCA mutation-positive ovarian cancer, with its capsule formulation already approved in the EU and USA.

The drug is currently undergoing extensive clinical trials for various cancers, including breast, gastric, and pancreatic cancers, indicating its potential broad application in oncology beyond ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: first global approval. Deeks, ED.[2020]

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]

Citations

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. France pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

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

Metformin Can Enhance the Inhibitory Effect of Olaparib in Bladder Cancer Cells. [2022]

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. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

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

Olaparib: first global approval. [2020]

10. 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]