Olaparib for Biliary Tract Cancer

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

36 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 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.

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.

What safety data exists for Olaparib in treating biliary tract cancer?

The safety data for Olaparib in biliary tract cancer is limited, as it is rarely evaluated in this type of cancer. However, ongoing clinical trials, such as NCT04298021, are assessing its efficacy and safety in combination with an ATR inhibitor. Olaparib has been tested in other cancers, like breast and ovarian cancer, where it has shown promising activity and has been approved for use, indicating a well-established safety profile in those contexts. ^{1 2 3 4 5}

Is the drug Olaparib a promising treatment for Biliary Tract Cancer?

Yes, Olaparib shows promise as a treatment for Biliary Tract Cancer, especially when used with another drug called ceralasertib. This combination has been shown to effectively slow down tumor growth in studies, making it a potential new option for patients. ^{2 6 7 8 9}

What data supports the idea that Olaparib for Biliary Tract Cancer is an effective drug?

The available research shows that Olaparib, when used alone, has moderate effects in stopping the growth of biliary tract cancer cells. However, when combined with another drug called ceralasertib, it significantly reduces tumor growth in lab models. This combination also shows positive results in ongoing clinical trials with patients, suggesting it could be a promising approach for treating biliary tract cancer. Compared to other treatments like pemigatinib, which extends survival to over 20 months for certain patients, and the standard gemcitabine-cisplatin therapy, which offers about 11.7 months of survival, the combination of Olaparib and ceralasertib shows potential but needs more research to confirm its effectiveness. ^{2 6 10 11 12}

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, 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]

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]

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 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]

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]

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 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]

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 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]

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]

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]

Citations

1. Ireland pubmed.ncbi.nlm.nih.gov

ATR inhibition amplifies antitumor effects of olaparib in biliary tract cancer. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Pemigatinib for adults with previously treated, locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions/rearrangements. [2022]

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

Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial. [2022]

4. England 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. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Regorafenib-avelumab combination in patients with biliary tract cancer (REGOMUNE): a single-arm, open-label, phase II trial. [2022]

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

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

7. England pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. [2020]

8. England pubmed.ncbi.nlm.nih.gov

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

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

Olaparib: first global approval. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Varlitinib plus capecitabine in second-line advanced biliary tract cancer: a randomized, phase II study (TreeTopp). [2022]

11. China pubmed.ncbi.nlm.nih.gov

Systemic therapy for biliary cancers. [2017]

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

Phase 2 study of copanlisib in combination with gemcitabine and cisplatin in advanced biliary tract cancers. [2022]