Olaparib for Pancreatic Cancer
Recruiting in Palo Alto (17 mi)
+357 other locations
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)
Must not be taking: CYP3A4/5 inhibitors
Disqualifiers: Neuroendocrine tumors, MDS, AML, others
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.
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.
What data supports the effectiveness of the drug Olaparib for pancreatic cancer?
Is Olaparib safe for use in humans?
Olaparib (Lynparza) has been tested in various clinical trials for conditions like ovarian and breast 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.12567
How does the drug olaparib differ from other treatments for pancreatic cancer?
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
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.
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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.
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Trial Timeline
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
Treatment Details
Interventions
- Olaparib (PARP Inhibitor)
Trial OverviewThe 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.
Participant Groups
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 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).
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.
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.
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.
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.
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.