Olaparib for Pancreatic Cancer

Recruiting at 379 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4/5 inhibitors

Disqualifiers: Neuroendocrine tumors, MDS, AML, others

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: 42

Duration: 12 months

152 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called olaparib to determine its effectiveness in treating pancreatic cancer that has been surgically removed and has specific genetic mutations (changes in BRCA1, BRCA2, or PALB2 genes). Olaparib, a type of targeted therapy, prevents cancer cells from repairing their damaged DNA, leading to cell death. The trial compares olaparib to a placebo, a pill that resembles the drug but contains no active ingredient. Individuals who have completed surgery and chemotherapy for pancreatic cancer and possess these genetic changes may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use certain medications that strongly inhibit CYP3A4/5 enzymes, like ketoconazole or ritonavir, while participating in the trial.

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

Research has shown that olaparib can be safe for people, but like any medicine, it can have some side effects. In previous studies, about 40% of people taking olaparib experienced serious side effects, compared to 23% of those who took a placebo (a harmless pill). These side effects can include nausea and lower levels of hemoglobin, a protein in red blood cells.

Olaparib is already used to treat some other types of cancer, so doctors have extensive experience with it and know what to monitor. However, it's important to remember that everyone's body reacts differently. What works well for one person might not work the same for another. Always consult a doctor about any concerns or questions before joining a trial. ^{1 2 3 4 5}

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

Unlike the standard treatments for pancreatic cancer, such as chemotherapy and surgery, olaparib is unique because it is a targeted therapy known as a PARP inhibitor. Most treatments for this condition focus on killing rapidly dividing cells, but olaparib works differently by targeting cancer cells' ability to repair their DNA, making it especially promising for patients with specific genetic mutations. Researchers are excited about olaparib because it offers a more personalized approach that could potentially lead to better outcomes with fewer side effects compared to traditional options.

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

Research has shown that Olaparib, a type of medication, can be effective for pancreatic cancer patients with certain genetic changes, such as BRCA1, BRCA2, or PALB2. In this trial, participants will receive either Olaparib or a placebo. Earlier studies found that about one in four patients with these genetic changes responded well to Olaparib, especially after platinum-based chemotherapy. For some, the cancer did not progress or lead to death when treated with Olaparib compared to those who received a placebo. Additionally, patients with a BRCA mutation experienced longer periods without disease progression when treated with Olaparib. These findings suggest that Olaparib may help slow cancer growth by preventing tumor cells from repairing their damaged DNA. ^{1 2 4 6 7}

Who Is on the Research Team?

Kim A Reiss Binder

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for adults in the US with resected pancreatic cancer and a BRCA1, BRCA2, or PALB2 mutation. They must have completed surgery and chemotherapy without recurrence of cancer. Participants need adequate blood counts, no serious medical conditions, not be on certain drugs that affect metabolism, and can't be pregnant or breastfeeding.

Inclusion Criteria

STEP 0 (PRE-REGISTRATION) INCLUSION CRITERIA

I have had or will have at least 3 months of chemotherapy around the time of my surgery.

I have recovered from side effects of previous cancer treatments, except for hair loss or nerve issues.

Exclusion Criteria

Patient must not be pregnant or breast-feeding due the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to Step 1 randomization to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

Patient is living outside the US

I do not have a neuroendocrine tumor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olaparib or placebo orally twice daily on days 1-28 of each cycle, repeating every 28 days for 12 cycles

12 months

Monthly visits for 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

Follow-up at 30 days, every 4 months for year 1, then every 6 months for years 2-10

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib

Trial Overview The study tests if olaparib after surgery and chemo extends survival in patients with specific genetic mutations linked to pancreatic cancer. Olaparib blocks an enzyme involved in DNA repair which may prevent tumor cells from surviving. Patients are randomly assigned to receive either olaparib or a placebo.

How Is the Trial Designed?

Group I: Arm I (olaparib) Experimental Treatment 4 Interventions

Patients receive olaparib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scans or CT/MRI and collection of blood throughout the study.

Group II: Arm II (placebo) Placebo Group 4 Interventions

Patients receive placebo PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scans or CT/MRI and collection of blood throughout the study.

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 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 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, 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 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]

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]

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, 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 (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]

Citations

1. 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 ...

2. 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.

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. 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%), ...