Olaparib for Pancreatic Cancer
Recruiting in Palo Alto (17 mi)
+359 other locations
KA
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?
Research Team
KA
Kim A Reiss Binder
Principal Investigator
ECOG-ACRIN Cancer Research Group
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
Trials
14080
Patients Recruited
41,180,000+
Findings from Research
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]
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]
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]
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]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
New Adjuvant Treatment for High-Risk Early Breast Cancer.Aschenbrenner, DS.[2022]
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
Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. [2022]
Olaparib in combination with irinotecan, cisplatin, and mitomycin C in patients with advanced pancreatic cancer. [2022]
Olaparib: first global approval. [2020]
Clinical Activity and Safety of Cediranib and Olaparib Combination in Patients with Metastatic Pancreatic Ductal Adenocarcinoma without BRCA Mutation. [2022]
Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer. [2016]
FDA Approval Summary: Olaparib Monotherapy in Patients with Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated with Three or More Lines of Chemotherapy. [2022]
New Adjuvant Treatment for High-Risk Early Breast Cancer. [2022]
Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. [2020]