What side effects are associated with this type of intervention?

Common treatments for bile duct cancer include chemotherapy regimens such as gemcitabine combined with cisplatin, and targeted therapies like PARP inhibitors (e.g., Olaparib). The side effects of these treatments can vary. For chemotherapy, common side effects include nausea, vomiting, fatigue, and hematologic toxicities such as anemia, thrombocytopenia, and neutropenia. PARP inhibitors like Olaparib can cause similar hematologic side effects, including anemia, thrombocytopenia, and neutropenia, as well as non-hematologic effects like nausea, anorexia, and asthenia. These side effects are generally manageable with dose modifications and supportive care.

What prior FDA approvals exist?

There is limited specific information on prior FDA approvals for PARP inhibitors like Olaparib in the treatment of bile duct cancer. However, Olaparib is being studied for its efficacy in treating metastatic biliary tract cancer with aberrant DNA repair gene mutations. Generally, treatments for advanced biliary tract cancers have included chemotherapy regimens such as gemcitabine combined with cisplatin, and newer approaches are exploring targeted therapies and immunotherapies.

What other types of research exist?

Promising novel alternatives to Olaparib for bile duct cancer patients include: <ol> <li>Pemigatinib - an FGFR inhibitor shown to be effective in patients with FGFR2 gene fusions.</li> <li></li> </ol> Ivosidenib - an IDH1 inhibitor for patients with IDH1 mutations. 3. Nivolumab - a PD-1 inhibitor that has shown efficacy in advanced refractory biliary tract cancer. 4. Durvalumab combined with gemcitabine and cisplatin - an immunotherapy approach that has shown promise in advanced biliary tract cancer.

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PARP Inhibitor

Olaparib for Biliary Tract Cancer

Q: What is the mechanism of action of this treatment?

The most common treatments for bile duct cancer include chemotherapy, targeted therapy, and PARP inhibitors like Olaparib. Chemotherapy drugs, such as gemcitabine and cisplatin, work by damaging the DNA of cancer cells, preventing them from dividing and growing. Targeted therapies, like FGFR inhibitors, block specific molecules involved in cancer cell growth and survival. PARP inhibitors, such as Olaparib, prevent the repair of single-strand DNA breaks in cancer cells with defective DNA repair mechanisms, leading to cell death. These treatments are significant for bile duct cancer patients as they offer tailored approaches that can improve outcomes, especially in those with specific genetic mutations.

Phase 2

Recruiting

Led By Daniel H Ahn

Research Sponsored by Academic and Community Cancer Research United

Eligibility Criteria Checklist

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

Must have

Histological or cytological documentation of metastatic adenocarcinoma of the biliary tract

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (=< 5 x ULN for subjects with liver involvement of their cancer)

Must not have

Concomitant use of known strong or moderate CYP3A inducers

Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial studies how well olaparib works in patients with advanced biliary tract cancer and specific DNA repair gene mutations. Olaparib may help stop cancer growth by blocking enzymes needed for cell repair. The trial aims to see if this treatment can improve survival and response rates.

Who is the study for?

Adults with metastatic biliary tract cancer and specific DNA repair gene mutations can join. They must have a certain level of blood cells, organ function, and life expectancy over 16 weeks. Participants need to provide samples for research and not be pregnant or breastfeeding. Those with severe heart conditions, recent surgeries, uncontrolled infections or hypertension, prior PARP inhibitor treatment like olaparib, other cancers or treatments within the last month are excluded.

What is being tested?

The trial is testing Olaparib's effectiveness on patients with advanced biliary tract cancer that has spread and who have abnormal DNA repair genes. It involves MRI and CT scans for monitoring tumor response to Olaparib which blocks enzymes needed by cancer cells to grow.

What are the potential side effects?

Olaparib may cause side effects such as nausea, vomiting, fatigue, anemia (low red blood cell counts), neutropenia (low white blood cell counts), thrombocytopenia (low platelet counts), digestive issues like indigestion or diarrhea, changes in taste sensation and risk of infection.

Eligibility Criteria

Inclusion Criteria

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

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My cancer, originating in the bile ducts, has spread to other parts.

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My liver enzymes are within the required range for the trial.

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I have genetic changes linked to how my cells repair DNA.

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My cancer can be measured by tests.

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My kidneys are functioning well, with a creatinine clearance of at least 51 mL/min.

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I am 18 years old or older.

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I can take care of myself and am up and about more than half of my waking hours.

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My hemoglobin level is at least 9.0 g/dL and I haven't had a blood transfusion in the last 28 days.

Exclusion Criteria

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

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I am not taking any strong or moderate drugs that affect liver enzymes.

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I understand the study drug's effects on unborn babies are unknown.

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I have not had major surgery or a serious injury in the last 28 days.

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I am immunocompromised or HIV positive and on antiretroviral therapy.

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I have previously been treated with a PARP inhibitor.

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I am experiencing moderate to severe dehydration.

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I require dialysis for kidney failure.

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I have a condition that affects how my body absorbs medication.

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I have been diagnosed with MDS/AML or show signs of it.

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I have or had a pheochromocytoma.

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I currently have symptoms of interstitial lung disease.

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I haven't had serious bleeding issues in the last month.

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I have heart failure that affects my daily activities.

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I am on medication that affects my heart's rhythm.

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I have fluid in my chest or abdomen causing significant breathing problems.

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My blood pressure is not controlled and is considered severe.

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I am on medication for seizures.

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My condition did not improve after platinum-based chemotherapy.

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I cannot take medicine by mouth.

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I have a wound, ulcer, or bone fracture that hasn't healed.

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I do not have a serious ongoing infection.

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I have had an organ transplant, bone marrow transplant, or cord blood transplantation.

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I am not taking strong or moderate CYP3A inhibitors.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years

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

Progression-free survival (PFS) at first scan

Secondary study objectives

Duration of response (DoR)

Incidence of adverse events

Objective response rate

+2 more

Other study objectives

Mutational signatures

Presence of mutations and mutational signatures

Prevalence of mutations

+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

1Treatment groups

Experimental Treatment

Group I: Treatment (olaparib)Experimental Treatment4 Interventions

Patients receive olaparib PO BID on days 1-28. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan or MRI throughout the trial, and collection of blood and tissue samples on study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Olaparib

2007

Completed Phase 4

~2190

Biospecimen Collection

2004

Completed Phase 3

~2030

Computed Tomography

2017

Completed Phase 2

~2790

Magnetic Resonance Imaging

2017

Completed Phase 3

~1180

0 / 31Eligibility 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 bile duct cancer include chemotherapy, targeted therapy, and PARP inhibitors like Olaparib. Chemotherapy drugs, such as gemcitabine and cisplatin, work by damaging the DNA of cancer cells, preventing them from dividing and growing. Targeted therapies, like FGFR inhibitors, block specific molecules involved in cancer cell growth and survival. PARP inhibitors, such as Olaparib, prevent the repair of single-strand DNA breaks in cancer cells with defective DNA repair mechanisms, leading to cell death. These treatments are significant for bile duct cancer patients as they offer tailored approaches that can improve outcomes, especially in those with specific genetic mutations.

Combining biological agents and chemotherapy in the treatment of cholangiocarcinoma.