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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether olaparib, a cancer drug, can effectively treat Pancreatic Acinar Cell Carcinoma (PACC), a rare and aggressive form of pancreatic cancer. The focus is on patients whose PACC hasn't responded to previous treatments and can't be treated with surgery. Participants will take olaparib orally twice a day in 28-day cycles and regularly visit the study site for monitoring. This trial suits adults with PACC who have tried other treatments without success and are unable to undergo surgery. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

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.

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

Research shows that olaparib, a drug being tested for pancreatic cancer, has been used in other studies and has some known side effects. One study found that about 40% of people taking olaparib experienced severe side effects, compared to 23% who took a placebo (a pill with no medicine). Common side effects included a drop in hemoglobin, which can lower energy levels, and nausea, which affected more than half of the patients in another study.

Although these side effects might seem concerning, olaparib is already approved for other uses. This approval means doctors have significant experience in managing these side effects. Understanding these details can help prospective trial participants make an informed decision. ^{1 2 3 4 5}

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

Olaparib is unique because it targets cancer cells in a new way as a PARP inhibitor. Unlike traditional chemotherapy for pancreatic cancer, which attacks all rapidly dividing cells, Olaparib specifically blocks an enzyme that cancer cells need to repair their damaged DNA. This means it has the potential to be more selective, causing less harm to healthy cells. Researchers are excited about Olaparib because it could offer a more targeted treatment option and may be particularly effective for patients with specific genetic mutations.

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

Research has shown that olaparib, the treatment under study in this trial, may help treat certain types of pancreatic cancer, particularly in patients with BRCA mutations. One study found that 32 out of 92 patients with a BRCA mutation who took olaparib did not experience cancer progression, compared to only 18 out of 62 patients who took a placebo. This suggests that olaparib might help control cancer for some individuals. Another study found that olaparib extended the time patients lived without their cancer worsening. While these results are promising, they primarily apply to individuals with specific genetic backgrounds, such as those with BRCA mutations. The effectiveness of olaparib in treating Pancreatic Acinar Cell Carcinoma (PACC) remains under investigation. ^{1 3 6 7 8}

Who Is on the Research Team?

Christine Alewine, MD, PhD

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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 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]

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]

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]

Citations

1. lynparza.com lynparza.com/pancreatic-cancer/results.html

Pancreatic Cancer Treatment Results 32 out of 92 adults with an inherited BRCA mutation did not have disease progression or death with LYNPARZA compared with 18 out of 62 adults with placebo.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8208637/

The Role of Olaparib in Metastatic Pancreatic Cancer - PMC Although the study met its primary endpoint, median OS was not statistically significant (18.9 months in Olaparib arm versus 18.1 months in placebo arm, HR 0.91 ...

3. lynparzahcp.com lynparzahcp.com/pancreatic-cancer/efficacy/polo.html

LYNPARZA Metastatic Pancreatic Cancer POLO Trial Efficacy ... Almost 1 in 4 patients in the LYNPARZA group with measurable disease after first-line platinum-based chemotherapy achieved a response (vs almost 1 in 8 in the ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1903387

Maintenance Olaparib for Germline BRCA-Mutated ... Among patients with a germline BRCA mutation and metastatic pancreatic cancer, progression-free survival was longer with maintenance olaparib than with placebo.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10896473/

Olaparib in Patients With Pancreatic Cancer With BRCA1/2 ... The collective results from these three studies along with this TAPUR cohort demonstrate that treatment with a PARPi achieves an OR rate of 16%-42% in patients ...

6. lynparzahcp.com lynparzahcp.com/pancreatic-cancer/safety-tolerability/polo.html

LYNPARZA Safety and Tolerability Data from POLO Trial Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA for PROfound were: decrease in hemoglobin (98%), decrease in ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10476841/

Overall Survival Results From the POLO Trial: A Phase III ... The phase III POLO study demonstrated significant progression-free survival (PFS) benefit for active olaparib maintenance therapy versus placebo.

8. lynparzaarguide.com lynparzaarguide.com/clinical-trials/onset-and-duration/clinical-trials-onset-and-duration-pancreatic-cancer

Pancreatic Cancer Clinical Trial Onsets and Duration Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the metastatic setting for OlympiAD were: nausea (58%), ...