What side effects are associated with this type of intervention?

Common treatments for bladder cancer, particularly those involving PARP inhibitors like Olaparib, often have side effects that include anemia, thrombocytopenia, and neutropenia. Other notable side effects can include nausea, fatigue, and decreased white-cell count. Additionally, there is a risk of myelodysplastic syndrome and acute myeloid leukemia with PARP inhibitors. For treatments involving chemotherapy, side effects may also include bleeding, hypertension, and gastrointestinal issues such as nausea and anorexia.

What prior FDA approvals exist?

The FDA has approved several treatments for bladder cancer, including immunotherapies and chemotherapies. Notably, pembrolizumab and atezolizumab are approved as second-line therapies for advanced urothelial carcinoma. Additionally, enfortumab vedotin has been approved for patients who have previously received platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor. While Olaparib, a PARP inhibitor, is being studied for its efficacy in treating bladder cancer with DNA-repair defects, it has not yet received FDA approval for this specific indication.

What other types of research exist?

Promising novel alternatives to Olaparib for bladder cancer patients include: 1) Enfortumab Vedotin, an antibody-drug conjugate targeting Nectin-4, which has shown efficacy in patients previously treated with platinum and PD-1/PD-L1 inhibitors. 2) Pembrolizumab, an anti-PD-1 therapy, which has demonstrated effectiveness as a second-line treatment. 3) Cabozantinib, a tyrosine kinase inhibitor, which has shown activity in platinum-refractory metastatic urothelial carcinoma. 4) Sacituzumab Govitecan, an antibody-drug conjugate targeting Trop-2, which has shown promise in patients progressing after platinum-based chemotherapy and checkpoint inhibitors.

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PARP Inhibitor

Olaparib for Bladder Cancer

Phase 2

Recruiting

Led By Andrea B Apolo

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Ability to understand and the willingness to sign a written informed consent document or patients with impaired decision making capacity (IDMC) if they are represented by a legally authorized representative (LAR)

Patients must have Clinical Laboratory Improvement Act (CLIA) testing and fit one of the following groups: Confirmed presence of a cancer-associated alteration considered pathogenic/likely pathogenic by FM and/or the Genetics Review Panel in specified genes or in one or more of the DNA-repair genes tested in the FoundationOne FoundationOneCDx (F1CDx) panel

Must not have

Uncontrolled concurrent disease or illness

Patients with myelodysplastic syndrome/acute myeloid leukemia; or baseline features suggestive of myelodysplastic syndrome or acute myelogenous leukemia on peripheral blood smear or bone marrow biopsy, if clinically indicated

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Olaparib may cause side effects such as nausea, fatigue, anemia (low red blood cell count), vomiting, diarrhea, loss of appetite, taste changes, indigestion or heartburn. Some people might experience more serious issues like lung problems or blood clots.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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My tests show a genetic change linked to cancer.

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My cancer can be measured and has been treated with platinum-based chemotherapy or immune therapy.

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My cancer diagnosis was confirmed through tissue examination.

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I am 18 years old or older.

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I can take pills and don't have stomach issues that affect medicine absorption.

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I can provide a previous tumor sample or am willing to have a biopsy for testing.

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I am postmenopausal or cannot become pregnant.

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I am fully active or able to carry out light work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any uncontrolled diseases or illnesses.

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

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I have brain metastases.

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I have a long-term or recent liver disease.

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I have not had any other cancer in the last 5 years.

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My ECG shows a QTc of more than 470 msec or I have a family history of long QT syndrome.

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I am not taking drugs that affect CYP3A enzyme activity.

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I do not have active hepatitis B or C.

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I have had a bone marrow or double cord blood transplant.

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

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I have previously been treated with olaparib or another PARP inhibitor.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall response rate (ORR)

Secondary study objectives

Incidence of adverse events

DNA

Overall survival (OS)

+1 more

Side effects data

From 2023 Phase 3 trial • 154 Patients • NCT02184195

49%

Nausea

47%

Fatigue

38%

Diarrhoea

29%

Abdominal pain

29%

Anaemia

28%

Constipation

27%

Decreased appetite

27%

Back pain

26%

Vomiting

21%

Arthralgia

19%

Pyrexia

18%

Asthenia

13%

Rash

13%

Nasopharyngitis

11%

Alanine aminotransferase increased

11%

Dyspnoea

10%

Neuropathy peripheral

10%

Cough

10%

Abdominal pain upper

10%

Dyspepsia

10%

Anxiety

10%

Pruritus

Hyperglycaemia

Dizziness

Aspartate aminotransferase increased

Thrombocytopenia

Oedema peripheral

Pain in extremity

Insomnia

Stomatitis

Dry mouth

Headache

Neutropenia

Blood creatinine increased

Weight decreased

Dysgeusia

Blood alkaline phosphatase increased

Neutrophil count decreased

Muscle spasms

Influenza

Influenza like illness

Myalgia

Peripheral sensory neuropathy

Gamma-glutamyltransferase increased

Hypertension

Platelet count decreased

Depression

Lymphopenia

Gastrooesophageal reflux disease

Abdominal distension

Musculoskeletal pain

Flank pain

Cholangitis

Flatulence

Paraesthesia

General physical health deterioration

Bladder papilloma

Pneumonia pneumococcal

Abdominal infection

Bartholinitis

Pneumonia

Cerebrovascular accident

Pneumothorax

Gastric varices haemorrhage

Large intestinal obstruction

Cholecystitis

Anastomotic haemorrhage

Device occlusion

Stent malfunction

Bronchiolitis

Empyema

Syncope

Incisional hernia

Device dislocation

Obstruction gastric

Cardiac failure

Vascular stenosis

Pleural effusion

Incarcerated inguinal hernia

Urinary tract infection

Hypothyroidism

Transient ischaemic attack

Infusion related reaction

Duodenal perforation

Melaena

Bile duct obstruction

Pancreatitis

100%

80%

60%

40%

20%

Study treatment Arm

Olaparib 300 mg Twice Daily (bd)

Placebo

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Bone Scan

2015

Completed Phase 2

~50

Biopsy

2014

Completed Phase 4

~1150

Biospecimen Collection

2004

Completed Phase 3

~2030

Bone Marrow Biopsy

2021

Completed Phase 3

~230

Computed Tomography

2017

Completed Phase 2

~2790

Magnetic Resonance Imaging

2017

Completed Phase 3

~1180

Positron Emission Tomography

2011

Completed Phase 2

~2200

Olaparib

2007

Completed Phase 4

~2190

0 / 20Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for bladder cancer include chemotherapy, immunotherapy, and targeted therapy. Chemotherapy works by killing rapidly dividing cancer cells, but it can also affect normal cells, leading to side effects. Immunotherapy, such as checkpoint inhibitors like pembrolizumab and atezolizumab, enhances the body's immune response against cancer cells. Targeted therapies, including PARP inhibitors like Olaparib, specifically inhibit proteins involved in DNA repair, causing cancer cells with DNA repair defects to die. This is particularly important for bladder cancer patients with specific genetic mutations, as it offers a more personalized and potentially effective treatment option with fewer side effects compared to traditional chemotherapy.

[The role of immunotherapy in the modern treatment of urothelial carcinoma].Emerging drugs for urothelial carcinoma.