Olaparib for Biliary Tract Cancer

Not currently recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Academic and Community Cancer Research United

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Congestive heart failure, Uncontrolled hypertension, Seizure disorder, 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: 3

Duration: Up to 36 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called olaparib for individuals with biliary tract cancer that has spread. Researchers aim to determine if olaparib can halt cancer cell growth by targeting specific enzymes necessary for their development. The trial seeks participants diagnosed with metastatic biliary tract cancer who have specific genetic mutations related to DNA repair. As a Phase 2 trial, olaparib has shown promise in earlier studies and now requires further testing in a larger group. Participants will take olaparib pills and undergo regular scans and tests to monitor the treatment's effects. This research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking cancer treatment advancements.

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

The trial protocol does not specify if you must stop all current medications. However, you must stop taking strong or moderate CYP3A inhibitors and inducers, as well as certain foods and products like grapefruits and pomegranates, before joining. There are specific washout periods: 2 weeks for strong CYP3A inhibitors, 5 weeks for enzalutamide or phenobarbital, 3 weeks for other CYP3A inducers, and 7 days for certain foods and medications that prolong the QTc interval.

Is there any evidence suggesting that olaparib is likely to be safe for humans?

Research has shown that olaparib has been tested in patients with advanced biliary tract cancers. In these studies, 25% of patients experienced serious side effects, classified as grade 3 or 4 in clinical trials. Although this might sound concerning, olaparib is already FDA-approved for other cancers, such as ovarian cancer, indicating its safety is well-documented.

Testing olaparib for biliary tract cancer in a Phase 2 trial suggests earlier studies have found it generally safe for people. However, like any treatment, side effects can occur, so discussing these with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for biliary tract cancer?

Olaparib is unique for biliary tract cancer treatment because it specifically targets and inhibits the enzyme PARP (poly ADP-ribose polymerase), which plays a role in DNA repair. Unlike traditional treatments like chemotherapy and radiation, which broadly attack rapidly dividing cells, olaparib offers a more targeted approach by exploiting flaws in cancer cells' DNA repair mechanisms. Researchers are excited about this because it holds the potential to be more effective with fewer side effects, offering a new hope for patients with this challenging condition.

What evidence suggests that olaparib might be an effective treatment for biliary tract cancer?

Research has shown that olaparib, which participants in this trial will receive, may help treat advanced biliary tract cancer. One study found that patients taking olaparib lived for an average of 11.2 months. The time patients lived without their cancer worsening, known as progression-free survival, was about 16.7 weeks. These findings suggest that olaparib could help manage the disease temporarily. Olaparib works by blocking certain enzymes that cancer cells need to grow, potentially stopping their growth. ^{1 2 5 6 7}

Who Is on the Research Team?

Daniel H Ahn

Principal Investigator

Academic and Community Cancer Research United

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

Women who can have children need to have a negative pregnancy test before starting the treatment.

Provide informed written consent

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

Exclusion Criteria

I haven't had cancer treatment or tumor-targeting procedures in the last 28 days.

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

I have not had a blood transfusion in the last 4 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olaparib orally twice daily on days 1-28, with treatment repeating every 28 days for up to 36 cycles

Up to 36 months

Monthly visits for treatment and imaging

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then every 3 months

Up to 3 years

Follow-up visits every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib

Trial Overview 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.

How Is the Trial Designed?

Group I: Treatment (olaparib) Experimental Treatment 4 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.

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?

Academic and Community Cancer Research United

Lead Sponsor

Trials

54

Recruited

4,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 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]

The addition of nab-paclitaxel to the standard gemcitabine-cisplatin therapy for advanced biliary tract cancers resulted in a median progression-free survival of 11.8 months and a median overall survival of 19.2 months, which are improvements over historical controls that only received gemcitabine-cisplatin.

Despite a high incidence of grade 3 or higher adverse events (58%), including neutropenia in 33% of patients, the treatment was generally well-tolerated, especially at reduced doses, indicating a potential for better management of side effects while improving survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial. Shroff, RT., Javle, MM., Xiao, L., et al.[2022]

In a phase II study involving 127 patients with advanced biliary tract cancer, the combination of varlitinib and capecitabine showed a modest objective response rate of 9.4%, compared to 4.8% for capecitabine alone, but did not significantly improve progression-free survival (PFS) or overall survival.

While the overall efficacy was similar to capecitabine alone, a subgroup analysis indicated potential PFS benefits for female patients and those with gallbladder cancer, suggesting that varlitinib may be more effective in these specific groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varlitinib plus capecitabine in second-line advanced biliary tract cancer: a randomized, phase II study (TreeTopp). Javle, MM., Oh, DY., Ikeda, M., et al.[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]

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]

Pemigatinib, an FGFR1-4 inhibitor, has shown promising results in extending median overall survival to over 20 months for patients with intrahepatic cholangiocarcinoma who have FGFR2 fusions, compared to the typical 1-year survival with current first-line treatments.

FGFR2 alterations are present in about 10-15% of intrahepatic cholangiocarcinoma cases, highlighting the potential for targeted therapies like pemigatinib to improve outcomes in this aggressive cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemigatinib for adults with previously treated, locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions/rearrangements. Walden, D., Eslinger, C., Bekaii-Saab, T.[2022]

In a Phase II study involving 43 patients with inoperable gall bladder or biliary tract cancer, the combination of capecitabine and oxaliplatin showed a modest overall response rate of 23.8% and a median overall survival of 7.9 months.

The treatment was well tolerated, with no severe neutropenia or thrombocytopenia reported, although some patients experienced grade 3/4 sensory neuropathy, indicating that while this regimen is less effective than the standard cisplatin and gemcitabine combination, it remains a viable option for patients who cannot receive those treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of capecitabine and oxaliplatin combination chemotherapy in patients with inoperable adenocarcinoma of the gall bladder or biliary tract. Graham, JS., Boyd, K., Coxon, FY., et al.[2021]

The combination of cisplatin and gemcitabine is established as the standard first-line treatment for biliary tract cancers, but overall clinical outcomes remain poor, highlighting the need for improved therapies.

Molecular profiling can identify genetic alterations in biliary cancers, guiding targeted therapies and immunotherapy, with ongoing research into actionable targets like FGFR2 fusions and IDH1/2 mutations showing promise for better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic therapy for biliary cancers. Jordan, E., Abou-Alfa, GK., Lowery, MA.[2017]

In a phase 2 study involving 24 patients with advanced biliary tract cancer, the addition of copanlisib, a PI3K inhibitor, to standard chemotherapy (gemcitabine and cisplatin) did not improve progression-free survival (PFS) at 6 months, which remained at 51%.

The study suggested that patients with low PTEN expression may benefit more from copanlisib treatment, as they had a longer median overall survival of 17.9 months compared to 7.0 months for those with high PTEN expression, indicating the potential for PTEN as a biomarker in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of copanlisib in combination with gemcitabine and cisplatin in advanced biliary tract cancers. Tan, ES., Cao, B., Kim, J., et al.[2022]

Olaparib, a PARP inhibitor, demonstrated moderate anti-tumor effects in biliary tract cancer (BTC) cell lines and increased levels of p-ATR and PD-L1, suggesting its potential as a treatment option.

The combination of olaparib with an ATR inhibitor (AZD6738) showed synergistic effects, significantly suppressing tumor growth in xenograft models and leading to downregulation of PD-L1 and YAP, indicating a promising therapeutic strategy for BTC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ATR inhibition amplifies antitumor effects of olaparib in biliary tract cancer. Nam, AR., Yoon, J., Jin, MH., et al.[2021]

In a phase II trial involving 34 patients with advanced biliary tract cancers, the combination of regorafenib and avelumab showed antitumor activity, with a partial response in 13.8% of patients and stable disease in 37.9%.

The treatment was associated with manageable safety concerns, primarily hypertension and fatigue, and the presence of certain biomarkers like high levels of programmed cell death ligand 1 was linked to better outcomes, suggesting potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib-avelumab combination in patients with biliary tract cancer (REGOMUNE): a single-arm, open-label, phase II trial. Cousin, S., Cantarel, C., Guegan, JP., et al.[2022]

Citations

1. nature.com nature.com/articles/s41698-025-01009-1

A phase II single-arm study of combination pembrolizumab ... A phase II single-arm study of combination pembrolizumab and olaparib in the treatment of patients with advanced biliary tract cancer.

2. dailyreporter.esmo.org dailyreporter.esmo.org/esmo-gastrointestinal-cancers-congress-2025/news/promising-activity-reported-for-olaparib-in-advanced-biliary-tract-cancers

Promising activity for olaparib in advanced biliary tract cancers Median overall survival was 11.2 months and median PFS was 16.7 weeks. Safety results showed that 25% of patients reported grade 3 or 4 ...

3. cancertherapyadvisor.com cancertherapyadvisor.com/reports/olaparib-biliary-tract-cancer-hrr-mutations/

Olaparib Proves Active in Advanced Biliary Tract Cancer ... The median follow-up for progression-free survival (PFS) was 16.1 weeks, and the median PFS was 16.7 weeks. The median overall survival was 11.2 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12354612/

The efficacy of olaparib as salvage therapy in an advanced ... Due to its highly invasive, occult, and heterogeneous nature, the prognosis is very poor, with a five-year survival rate of approximately 5% (Zhang et al., 2021) ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04306367

Study of Pembrolizumab and Olaparib in Bile Duct Cancer The primary objective of the study is to assess the ORR of patients with advanced cholangiocarcinoma receiving a combination of pembrolizumab and olaparib.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39917990/

Olaparib in treatment-refractory isocitrate dehydrogenase 1 ... Results: NCI 10129 enrolled 30 patients with IDH-mutant CCA with no objective responses seen, and recruitment was closed early. Median ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.4087

Phase II clinical trial of olaparib plus pembrolizumab in the ... Results: Of 21 eligible patients, 14 were accrued between June 2020 and March 2022, and 13 were evaluable for efficacy. Patients had a median ...