Olaparib for Bladder Cancer
Recruiting in Palo Alto (17 mi)
+17 other locations
Overseen byAndrea B Apolo
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
Must not be taking: CYP3A inhibitors/inducers
Disqualifiers: Brain metastases, Liver disease, Stroke, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
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.
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.
12345Is 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.
12678How 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.
124910Eligibility Criteria
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
+17 more
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.
+15 more
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 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Cohort II (biospecimen collection)Experimental Treatment7 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 Treatment8 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Colorado HospitalAurora, CO
Laura and Isaac Perlmutter Cancer Center at NYU LangoneNew York, NY
Huntsman Cancer Institute/University of UtahSalt Lake City, UT
Los Angeles General Medical CenterLos Angeles, CA
More Trial Locations
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. [2022]The PARP inhibitor olaparib (Lynparza™) demonstrates antitumor activity in women with relapsed ovarian cancer and a germline BRCA1/2 mutation (gBRCAm). Data from olaparib monotherapy trials were used to explore the treatment effect of olaparib in patients with gBRCAm ovarian cancer who had received multiple lines of prior chemotherapy.
Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer. [2022]Olaparib (Lynparza®) is a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor approved for first-line maintenance treatment in adults with advanced ovarian cancer who are in complete or partial response to first-line, platinum-based chemotherapy. Originally approved as monotherapy, olaparib is also approved to be administered in combination with bevacizumab in patients whose cancer is associated with homologous recombination deficiency (HRD), defined by either a BRCA1/2 mutation and/or genomic instability. In phase III trials, olaparib monotherapy significantly improved progression-free survival (PFS) relative to placebo (SOLO-1), as did olaparib plus bevacizumab relative to placebo plus bevacizumab (PAOLA-1), in patients with advanced ovarian cancer who had responded to platinum-based chemotherapy. In PAOLA-1, improvements in PFS with olaparib plus bevacizumab were not seen in patients with HRD-negative tumours relative to placebo plus bevacizumab. Both olaparib monotherapy and olaparib in combination with bevacizumab had generally manageable tolerability profiles. Olaparib, alone or in combination with bevacizumab, is a useful option for the first-line maintenance treatment of adults with HRD-positive, advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line, platinum-based chemotherapy.
Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer. [2016]Olaparib (Lynparza™; AZD2281) is a potent PARP-1 and PARP-2 inhibitor with biologic activity in ovarian cancer as well as other solid tumors. It has been tested in Phase I and II trials and has single-agent activity in both germline BRCA mutated and sporadic ovarian cancer. Phase III trials assessing the efficacy of olaparib in the maintenance setting following first line and platinum-sensitive recurrence are underway for patients with a germline BRCA mutation, given the inherent molecular compatibility with the drug's mechanism of action.
Olaparib: a review of its use as maintenance therapy in patients with ovarian cancer. [2016]Olaparib (Lynparza™) is a first-in-class, orally-active, small molecule, poly (ADP-ribose) polymerase inhibitor that induces synthetic lethality in homozygous BRCA-deficient cells. In the EU, the capsule formulation of olaparib is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive, relapsed, BRCA-mutated (germline and/or somatic), high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. This approval was based on the results of study 19, a randomized phase II trial in 265 patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer (HGSOC) who had received two or more platinum-based regimens and who had a partial or complete response to their most recent platinum-based regimen. Study 19 met its primary endpoint by demonstrating a significant improvement in progression-free survival in patients receiving olaparib compared with those receiving placebo. Moreover, a preplanned retrospective analysis identified those patients with a BRCA mutation (who comprised one-half of the overall study population) as being the subgroup that derived the greatest clinical benefit from olaparib. Single-agent olaparib was generally well tolerated, with the majority of adverse events being of mild to moderate severity and not requiring interruption of treatment. Fatigue, anaemia and neutropenia were the most frequently reported severe (grade ≥3) adverse events. An as yet unapproved tablet formulation of olaparib that has a lower pill burden than the capsule formulation is currently being investigated in phase III clinical studies.
Metformin Can Enhance the Inhibitory Effect of Olaparib in Bladder Cancer Cells. [2022]Bladder cancer is a common urinary system tumor. In the treatment of clinical patients, it is particularly important to find an effective treatment method to inhibit tumor growth. The world's first PARP inhibitor olaparib is mainly used for the treatment of BRCA1/BRCA2 mutated tumors. Metformin, an antidiabetic drug, has been reported to reduce cancer incidence in humans and improve survival in cancer patients.
FDA Approval Summary: Olaparib Monotherapy in Patients with Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated with Three or More Lines of Chemotherapy. [2022]On December 19, 2014, the FDA approved olaparib capsules (Lynparza; AstraZeneca) for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. The BRACAnalysis CDx (Myriad Genetic Laboratories, Inc.) was approved concurrently. An international multicenter, single-arm trial enrolled 137 patients with measurable gBRCAm-associated ovarian cancer treated with three or more prior lines of chemotherapy. Patients received olaparib at a dose of 400 mg by mouth twice daily until disease progression or unacceptable toxicity. The objective response rate (ORR) was 34% with median response duration of 7.9 months in this cohort. The most common adverse reactions (≥20%) in patients treated with olaparib were anemia, nausea, fatigue (including asthenia), vomiting, diarrhea, dysgeusia, dyspepsia, headache, decreased appetite, nasopharyngitis/pharyngitis/upper respiratory infection, cough, arthralgia/musculoskeletal pain, myalgia, back pain, dermatitis/rash, and abdominal pain/discomfort. Myelodysplatic syndrome and/or acute myeloid leukemia occurred in 2% of the patients enrolled on this trial.
Systematic Review of Olaparib in the Treatment of Recurrent Platinum Sensitive Ovarian Cancer. [2022]To systematically evaluate the efficacy and safety of olaparib in the treatment of recurrent platinum-sensitive ovarian cancer.
New Adjuvant Treatment for High-Risk Early Breast Cancer. [2022]Olaparib (Lynparza) is now approved for the adjuvant treatment of adult patients who have, or are suspected to have, the germline variation of BRCA-mutated human epidermal growth factor receptor 2-negative high-risk early breast cancer and who were previously treated with neoadjuvant or adjuvant chemotherapy.
Olaparib: first global approval. [2020]Olaparib (Lynparza™) is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor being developed by AstraZeneca for the treatment of solid tumours. The primary indication that olaparib is being developed for is BRCA mutation-positive ovarian cancer. A capsule formulation of the drug has received approval for use in this setting in the EU and USA, and a tablet formulation is in global phase III trials (including in the USA, EU, Australia, Brazil, Canada, China, Israel, Japan, Russia and South Korea). In addition, phase III trials in breast, gastric and pancreatic cancer are underway/planned, and phase I/II investigation is being conducted in other malignancies, including prostate cancer, non-small cell lung cancer, Ewing's sarcoma and advanced cancer. This article summarizes the milestones in the development of olaparib leading to this first approval for ovarian cancer.
Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. [2020]The poly(ADP-ribose) polymerase inhibitor olaparib (Lynparza™) is approved for maintenance treatment of platinum-sensitive relapsed ovarian cancer. OPINION is a single-arm, open-label, multicenter, Phase IIIb study to assess the efficacy and safety of olaparib tablet maintenance therapy in women with high-grade serous or endometrioid platinum-sensitive relapsed ovarian cancer without a germline BRCA1 or BRCA2 mutation. Eligible patients should have received ≥2 prior lines of platinum-based chemotherapy and be in complete or partial response following their most recent course or have no evidence of disease. Patients will receive olaparib tablets (300 mg twice daily) until disease progression, unacceptable toxicity or another discontinuation criterion. The primary end point is investigator-assessed progression-free survival; secondary end points include progression-free survival according to tumor homologous recombination deficiency status. Clinical trial registration: NCT03402841.