Olaparib for Pancreatic Cancer
Palo Alto (17 mi)Overseen byKim A Reiss Binder
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
Prior Safety Data
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?This phase II trial investigates how well the addition of olaparib following completion of surgery and chemotherapy works in treating patients with pancreatic cancer that has been surgically removed (resected) and has a pathogenic mutation in BRCA1, BRCA2, or PALB2. Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep tumor cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy.
Is the drug Olaparib a promising treatment for pancreatic cancer?Yes, Olaparib is a promising drug for pancreatic cancer, especially for patients with specific genetic mutations (BRCA mutations). It has shown activity in treating advanced pancreatic cancer and is being tested in clinical trials.12568
What data supports the idea that Olaparib for Pancreatic Cancer (also known as: Olaparib, Lynparza) is an effective treatment?The available research shows that Olaparib has shown signs of activity in patients with BRCA mutations and pancreatic ductal adenocarcinoma (PDAC). However, when combined with another drug, Cediranib, it did not show meaningful results in patients without BRCA mutations. This suggests that Olaparib might be more effective for pancreatic cancer patients with specific genetic mutations, but more research is needed to confirm its effectiveness compared to other treatments.12457
Do I need to stop my current medications for the trial?The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use known potent CYP3A4/5 inhibitors like ketoconazole or ritonavir during the trial.
What safety data is available for Olaparib (Lynparza)?Olaparib (Lynparza) has been tested in various clinical trials, primarily for ovarian cancer and other solid tumors. In a trial for advanced ovarian cancer, common adverse reactions (≥20%) included anemia, nausea, fatigue, vomiting, diarrhea, and others. Serious conditions like myelodysplastic syndrome and/or acute myeloid leukemia occurred in 2% of patients. These findings provide insight into the safety profile of Olaparib.23458
Eligibility Criteria
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
I am able to get out of my bed or chair and move around.
I had surgery for pancreatic cancer and currently show no signs of the cancer returning.
I am 18 years old or older.
I had hepatitis C but am cured, or I'm being treated with no detectable virus.
My hemoglobin level is at least 9.0 g/dL without recent blood transfusions.
I agree to genetic testing if my cancer has specific mutations.
I am not taking strong medications like ketoconazole or ritonavir.
I can understand and am willing to sign the consent form, or have someone legally authorized to do so on my behalf.
My pancreatic cancer did not worsen while I was on platinum-based therapy.
I do not have any serious health issues that are not under control.
I had surgery for pancreatic cancer and currently show no signs of the cancer returning.
I have a confirmed harmful mutation in BRCA1, BRCA2, or PALB2.
My scans show no signs of pancreatic cancer spread as of the last 4 weeks.
My hepatitis B virus load is undetectable with treatment.
Exclusion Criteria
I do not have a neuroendocrine tumor.
I have never had myelodysplastic syndrome or acute myeloid leukemia.
Treatment Details
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Arm I (olaparib)Experimental Treatment4 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 Group4 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.
Find a clinic near you
Research locations nearbySelect from list below to view details:
Saint Mary Medical CenterHobart, IN
Medical Oncology and Hematology Associates-LaurelDes Moines, IA
Chelsea HospitalChelsea, MI
Saint Vincent Hospital Cancer Center Green BayGreen Bay, WI
More Trial Locations
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Who is running the clinical trial?
National Cancer Institute (NCI)Lead Sponsor
References
Olaparib: first global approval. [2020]Olaparib (Lynparza™) is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor being developed by AstraZeneca for the treatment of solid tumours. The primary indication that olaparib is being developed for is BRCA mutation-positive ovarian cancer. A capsule formulation of the drug has received approval for use in this setting in the EU and USA, and a tablet formulation is in global phase III trials (including in the USA, EU, Australia, Brazil, Canada, China, Israel, Japan, Russia and South Korea). In addition, phase III trials in breast, gastric and pancreatic cancer are underway/planned, and phase I/II investigation is being conducted in other malignancies, including prostate cancer, non-small cell lung cancer, Ewing's sarcoma and advanced cancer. This article summarizes the milestones in the development of olaparib leading to this first approval for ovarian cancer.
Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer. [2016]Olaparib (Lynparza™; AZD2281) is a potent PARP-1 and PARP-2 inhibitor with biologic activity in ovarian cancer as well as other solid tumors. It has been tested in Phase I and II trials and has single-agent activity in both germline BRCA mutated and sporadic ovarian cancer. Phase III trials assessing the efficacy of olaparib in the maintenance setting following first line and platinum-sensitive recurrence are underway for patients with a germline BRCA mutation, given the inherent molecular compatibility with the drug's mechanism of action.
FDA Approval Summary: Olaparib Monotherapy in Patients with Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated with Three or More Lines of Chemotherapy. [2022]On December 19, 2014, the FDA approved olaparib capsules (Lynparza; AstraZeneca) for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. The BRACAnalysis CDx (Myriad Genetic Laboratories, Inc.) was approved concurrently. An international multicenter, single-arm trial enrolled 137 patients with measurable gBRCAm-associated ovarian cancer treated with three or more prior lines of chemotherapy. Patients received olaparib at a dose of 400 mg by mouth twice daily until disease progression or unacceptable toxicity. The objective response rate (ORR) was 34% with median response duration of 7.9 months in this cohort. The most common adverse reactions (≥20%) in patients treated with olaparib were anemia, nausea, fatigue (including asthenia), vomiting, diarrhea, dysgeusia, dyspepsia, headache, decreased appetite, nasopharyngitis/pharyngitis/upper respiratory infection, cough, arthralgia/musculoskeletal pain, myalgia, back pain, dermatitis/rash, and abdominal pain/discomfort. Myelodysplatic syndrome and/or acute myeloid leukemia occurred in 2% of the patients enrolled on this trial.
Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. [2022]The PARP inhibitor olaparib (Lynparza™) demonstrates antitumor activity in women with relapsed ovarian cancer and a germline BRCA1/2 mutation (gBRCAm). Data from olaparib monotherapy trials were used to explore the treatment effect of olaparib in patients with gBRCAm ovarian cancer who had received multiple lines of prior chemotherapy.
Olaparib in combination with irinotecan, cisplatin, and mitomycin C in patients with advanced pancreatic cancer. [2022]Olaparib is an oral inhibitor of polyadenosine 5'-diphosphoribose polymerization (PARP) that has previously shown signs of activity in patients with BRCA mutations and pancreatic ductal adenocarcinoma (PDAC).
Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. [2020]Olaparib (Lynparza™) is a PARP inhibitor approved for advanced BRCA-mutated (BRCAm) ovarian cancer. PARP inhibitors may benefit patients whose tumours are dysfunctional in DNA repair mechanisms unrelated to BRCA1/2. We report exploratory analyses, including the long-term outcome of candidate biomarkers of sensitivity to olaparib in BRCA wild-type (BRCAwt) tumours.
Clinical Activity and Safety of Cediranib and Olaparib Combination in Patients with Metastatic Pancreatic Ductal Adenocarcinoma without BRCA Mutation. [2022]Cediranib and olaparib combination did not result in clinically meaningful activity in patients with metastatic pancreatic ductal adenocarcinoma without known BRCA mutation.
New Adjuvant Treatment for High-Risk Early Breast Cancer. [2022]Olaparib (Lynparza) is now approved for the adjuvant treatment of adult patients who have, or are suspected to have, the germline variation of BRCA-mutated human epidermal growth factor receptor 2-negative high-risk early breast cancer and who were previously treated with neoadjuvant or adjuvant chemotherapy.