Olaparib for Pancreatic Cancer

Overseen By NCI Medical Oncology Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: HIV, Hepatitis B/C, Heart failure, 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: 11

Duration: Up to 2 years

20 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Pancreatic Acinar Cell Carcinoma (PACC) is a rare pancreatic tumor. People with PACC usually present with advanced disease, and their prognosis is poor. Researchers want to learn if a cancer drug called olaparib can help. Objective: To see if olaparib is an effective treatment for PACC. Eligibility: People aged 18 and older with PACC whose cancer did not respond to previous treatments or is not eligible for surgery. Design: Participants will be screened with the following: Medical history Physical exam Blood and urine tests Electrocardiogram (to test heart function) Computed tomography (CT) scans Pregnancy test (if needed) Tumor biopsy (if a sample is not available) Treatment will be given in 28-day cycles. Participants will take olaparib by mouth twice daily for each cycle. They will keep a medicine diary. They will receive treatment for up to 2 years. They may stop treatment early if their cancer gets worse or they have serious side effects. Participants will have study visits at the beginning of each cycle. At visits, they will repeat some screening tests. They will be asked about any changes in medicines they are taking and how they are feeling. They will have CT scans every 8 weeks starting in cycle 2. Participants will give blood samples for research. They may have optional tumor biopsies. Participants will have 2 follow-up visits in the 30 days after treatment ends or before they begin a new anti-cancer treatment. Then they will be contacted every 3 months by phone for 1 year. Participation will last for up to 3 years.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting treatment. You must stop using strong or moderate CYP3A inhibitors and inducers at least 2 to 5 weeks before starting the trial, depending on the specific medication.

What data supports the effectiveness of the drug Olaparib for pancreatic cancer?

Olaparib has shown activity in patients with pancreatic cancer who have BRCA mutations, similar to its effectiveness in treating ovarian cancer with the same genetic mutations. ^{1 2 3 4 5}

Is Olaparib safe for humans?

Olaparib (also known as Lynparza) has been tested in various clinical trials for different cancers, including ovarian and pancreatic cancer. Common side effects include nausea, fatigue, and anemia (low red blood cell count), while more serious effects like myelodysplastic syndrome (a blood disorder) and acute myeloid leukemia (a type of blood cancer) occurred in a small percentage of patients. ^{1 4 5 6 7}

How is the drug Olaparib unique in treating pancreatic cancer?

Olaparib is unique because it is an oral drug that targets specific genetic mutations (BRCA mutations) in pancreatic cancer, working by inhibiting PARP enzymes which help repair DNA damage in cancer cells, potentially making it more effective for certain patients compared to standard treatments. ^{1 2 4 7 8}

Research Team

Christine Alewine, MD, PhD

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults with advanced Pancreatic Acinar Cell Carcinoma (PACC) who have tried other treatments without success or can't undergo surgery. They must be at least 18, not pregnant, and agree to use contraception. Participants need measurable disease per specific criteria, adequate organ function, and no recent major surgeries or investigational therapies.

Inclusion Criteria

I haven't taken strong or moderate CYP3A inhibitors in the last 2 weeks.

I have recovered from recent surgeries and it's been over 2 weeks since any minor procedure.

My kidneys are functioning well enough, based on a calculation involving my age, weight, and gender.

Exclusion Criteria

I have no severe side effects from past cancer treatments.

I have been diagnosed with superior vena cava syndrome.

I have symptoms of heart failure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive olaparib by mouth twice daily in 28-day cycles for up to 2 years

Up to 2 years

Study visits at the beginning of each cycle, CT scans every 8 weeks starting in cycle 2

Follow-up

Participants have 2 follow-up visits in the 30 days after treatment ends, then contacted every 3 months by phone for 1 year

1 year

2 visits (in-person), phone contact every 3 months

Treatment Details

Interventions

• Olaparib

Trial Overview The trial is testing the effectiveness of olaparib for PACC in adults. Olaparib will be taken orally twice daily in cycles of 21 days for up to two years unless side effects become severe or cancer worsens. The study includes regular check-ups, blood tests, CT scans every eight weeks starting from cycle two, and optional tumor biopsies.

Participant Groups

Group I: Arm 1 Experimental Treatment 1 Intervention

Olaparib, taken orally, twice daily

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase 1 trial involving 18 patients with unresectable pancreatic ductal adenocarcinoma (PDAC), the maximum tolerated dose of olaparib combined with irinotecan and cisplatin was determined to be 100 mg twice daily, but the addition of mitomycin C was not tolerated due to high toxicity.

Despite significant toxicity, including a high rate of grade ≥3 adverse events in 89% of patients, one patient with a BRCA2 mutation experienced a durable response lasting over four years, suggesting that further investigation into PARP inhibitors for PDAC may be warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib in combination with irinotecan, cisplatin, and mitomycin C in patients with advanced pancreatic cancer. Yarchoan, M., Myzak, MC., Johnson, BA., 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]

The combination of cediranib and olaparib did not show clinically meaningful activity in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who do not have a known BRCA mutation, as no objective responses were observed in the study of 19 patients.

Despite some patients experiencing stable disease for a median of 3.1 months, the overall survival was only 3.4 months, indicating limited efficacy of this treatment combination in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Cediranib and Olaparib Combination in Patients with Metastatic Pancreatic Ductal Adenocarcinoma without BRCA Mutation. Kim, JW., Cardin, DB., Vaishampayan, UN., et al.[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]

Olaparib, a PARP inhibitor, showed a 36% objective response rate in women with relapsed ovarian cancer and a germline BRCA1/2 mutation, even after they had undergone multiple lines of chemotherapy, indicating its efficacy in this challenging patient population.

The median duration of response to olaparib was 7.4 months, and the safety profile was consistent across patients who had received three or more lines of prior chemotherapy, with similar rates of serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Matulonis, UA., Penson, RT., Domchek, SM., et al.[2022]

Olaparib, approved by the FDA for patients with advanced ovarian cancer carrying BRCA mutations, showed a 34% objective response rate in a trial of 137 patients who had undergone three or more prior chemotherapy treatments, with a median response duration of 7.9 months.

Common side effects included anemia, nausea, and fatigue, with a small risk (2%) of developing myelodysplastic syndrome or acute myeloid leukemia, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Olaparib Monotherapy in Patients with Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated with Three or More Lines of Chemotherapy. Kim, G., Ison, G., McKee, AE., 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]

References

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

Olaparib in combination with irinotecan, cisplatin, and mitomycin C in patients with advanced pancreatic cancer. [2022]

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

Olaparib: first global approval. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Cediranib and Olaparib Combination in Patients with Metastatic Pancreatic Ductal Adenocarcinoma without BRCA Mutation. [2022]

4. England pubmed.ncbi.nlm.nih.gov

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

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

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. [2022]

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

FDA Approval Summary: Olaparib Monotherapy in Patients with Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated with Three or More Lines of Chemotherapy. [2022]

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

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

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

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