Testing the Addition of Pembrolizumab, an Immunotherapy Cancer Drug to Olaparib Alone as Therapy for Patients With Pancreatic Cancer That Has Spread With Inherited BRCA Mutations
A
Anita Turk, MD
Primary Investigator
Overview
This phase II trial studies whether adding pembrolizumab to olaparib (standard of care) works
better than olaparib alone in treating patients with pancreatic cancer with germline BRCA1 or
BRCA2 mutations that has spread to other places in the body (metastatic). BRCA1 and BRCA2 are
human genes that produce tumor suppressor proteins. These proteins help repair damaged
deoxyribonucleic acid (DNA) and, therefore, play a role in ensuring the stability of eachgenetic material. When either of these genes is mutated, or altered, such that itsduct is not made or does not function correctly, DNA damage may not be repairedy. As a result, cells are more likely to develop additional genetic alterations thatd to some types of cancer, including pancreatic cancer. Immunotherapy with monoclonalbodies, such as pembrolizumab, may help the body's immune system attack the cancer, andy interfere with the ability of tumor cells to grow and spread. Olaparib is an inhibitor of
PARP, a protein that helps repair damaged DNA. Blocking PARP may help keep tumor cells fromg their damaged DNA, causing them to die. PARP inhibitors are a type of targetedherapy. The addition of pembrolizumab to the usual treatment of olaparib may help to shrinkumors in patients with metastatic pancreatic cancer with BRCA1 or BRCA2 mutations.
Description
PRIMARY OBJECTIVE:
I. To evaluate the progression free survival (PFS) of advanced pancreatic cancer patients
with germline BRCA1 or BRCA2 mutations treated with olaparib + pembrolizumab compared tob alone as maintenance therapy.
SECONDARY OBJECTIVES:
I. To evaluate the safety and tolerability associated with the combination of olaparib +brolizumab versus (vs.) olaparib alone as maintenance therapy.
II. To evaluate the overall survival (OS) of patients treated with olaparib + pembrolizumabd to olaparib alone as maintenance therapy.
III. To evaluate the overall response rate (ORR) by Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1, including confirmed and unconfirmed, complete and partial response, ofd with olaparib + pembrolizumab compared to olaparib alone, in the subset ofwith measurable disease.
IV. To evaluate the overall response rate (ORR) by immune RECIST, including confirmed and
unconfirmed, complete and partial response, of patients treated with olaparib + pembrolizumabd to olaparib alone, in the subset of patients with measurable disease.
V. To evaluate the duration of response (DoR) by RECIST 1.1 in patients treated with olaparib
+ pembrolizumab compared to olaparib alone.
BANKING OBJECTIVE:
I. To bank tissue and blood specimens for future correlative studies.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive olaparib orally (PO) twice daily (BID) on days 1-21 and pembrolizumabvenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 18ycles in the absence of disease progression or unacceptable toxicity. Beginning in cycle 19,ve olaparib PO BID on days 1-42 and pembrolizumab IV over 30 minutes on day 1.
Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive olaparib PO BID on days 1-21. Cycles repeat every 21 days in thebsence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed for 30 days and every 6 months for
3 years from the date of randomization.
Eligibility
You may be eligible for this study if you meet the following criteria:
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Conditions:
Metastatic Pancreatic Adenocarcinoma, Stage IV Pancreatic Cancer AJCC v8
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Age: 18 Years
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Gender: All
Inclusion Criteria:
- Patient must have a histologic or cytologic diagnosis of pancreatic adenocarcinoma.Patients with neuroendocrine tumors, acinar cell and adenosquamous carcinomas areuded. All disease must be assessed and documented on the Baseline Tumor AssessmentForm
- Patients must have one of the following mutations: germline mutation in BRCA 1 or 2hat was tested in a Clinical Laboratory Improvement Act (CLIA) certified lab definedve and/or deleterious (that is, pathogenic or likely pathogenic variant).(NOTE: Patients with tumor somatic mutations are not eligible)
- Patient must have metastatic disease and received first line platinum-basedhemotherapy (i.e. fluorouracil, irinotecan, leucovorin and oxaliplatin [FOLFIRINOX],ucovorin calcium, 5-fluorouracil, and oxaliplatin [FOLFOX], gemcitabine +b-paclitaxel + cisplatin or gemcitabine + cisplatin)
- Patients must have had a computed tomography (CT) or magnetic resonance imaging (MRI)howing stable or responding disease on first line platinum-based chemotherapy within30 days prior to registration
- Patients with known human immunodeficiency virus (HIV)-infection are eligibleviding they are on effective anti-retroviral therapy and have undetectable virald at their most recent viral load test and within 6 months prior to registration
- Patients with history of chronic hepatitis B virus (HBV) infection must haveundetectable HBV viral load within 30 days prior to registration
- Patients with a history of hepatitis C virus (HCV) infection must have been treatedd cured. For patients with HCV infection who are currently on treatment must have anundetectable HCV viral load within 30 days prior to registration
- Patients must have received at least 16 weeks of first line platinum-basedhemotherapy for metastatic disease. Patients may have also received one cycle of(no more than 4 weeks) with gemcitabine + nab-paclitaxel while waiting forgermline test results, prior to platinum-based therapy
- Patients' last chemotherapy treatment must be within 30 days prior to registration
- Patients must have resolved or stable =< grade 1 toxicity from prior administration ofher investigational drug and/or prior anti-cancer treatment, excluding neuropathyd alopecia
- Zubrod performance status of 0-1
- Patients must be >= 18 years old
- Patients must have a complete medical history and physical exam within 28 days priorgistration
- Absolute neutrophil count >= 1.5 x 10^3/uL (within 14 days of registration)
- Platelets >= 100 x 10^3/uL (within 14 days of registration)
- Total bilirubin =< 1.5 institutional upper limit of normal (ULN) (within 14 days ofgistration)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutionalLN (within 14 days of registration)
- Albumin >= 3.0 g/dL (within 14 days of registration)
- Hemoglobin >= 9.0 g/dL (within 14 days of registration)
- Participants must have a serum creatinine =< the institutional (I)ULN OR measured ORulated creatinine clearance >= 50 mL/min using the following Cockcroft-GaultFormula. This specimen must have been drawn and processed within 14 days prior togistration
- Patients must have CA19-9 obtained within 42 days prior to registration
- Patients must be able to swallow and retain oral medications and have no knowngastrointestinal disorders likely to interfere with absorption of the study medication
- Participants with a prior or concurrent malignancy whose natural history or treatment(in the opinion of the treating physician) does not have the potential to interferewith the safety or efficacy assessment of the investigational regimen are eligible forhis trial provided it does not require concurrent therapy
- Patients must be offered the opportunity to participate in specimen banking ofd paraffin-embedded (FFPE) tissue and whole blood. If a patient is unableubmit archival tissue, should the patient need to undergo a standard of carebiopsy per National Comprehensive Cancer Network (NCCN) guidelines, patients must thenbe offered the opportunity to submit the fresh tumor tissue from that biopsy. Withust be collected and submitted via the Southwestgy Group (SWOG) Specimen Tracking System
- Patients must be informed of the investigational nature of this study and must signd give informed consent in accordance with institutional and federal guidelines. Forwith impaired decision making capabilities, legally authorizedves may sign and give informed consent on behalf of study participants indance with applicable federal, local, and Canada Industrial Relations Board(CIRB) regulations
- As a part of the Oncology Patient Enrollment Network (OPEN) registration process theg institution's identity is provided in order to ensure that the current(within 365 days) date of institutional review board approval for this study has beend in the system
Exclusion Criteria:
- Patients must not have a known hypersensitivity to olaparib or any of the excipientshe product
- Patients must not be planning to receive strong or moderate CYP3A inhibitors orducers while on olaparib treatment. Patients receiving strong or moderate CYP3Ahibitors must discontinue use at least 2 weeks prior to receiving olaparib. Patientsving strong or moderate CYP3A inducers must discontinue use at least 5 weeksving olaparib. Medications should be checked using a frequently updateddical reference for a list of drugs to avoid
- Patients must not have received live vaccines within 42 days prior to randomizationd must not be planning to receive live virus or live bacterial vaccines whileving study treatment and during the 30 day follow up period. Examples of livevaccines include, but are not limited to, the following: measles, mumps, rubella,hicken pox, shingles, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), andyphoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killedvirus vaccines and are allowed; however, intranasal influenza vaccines (e.g.,Flu-Mist) are live attenuated vaccines, and are not allowed. Coronavirus disease 2019(COVID-19) messenger ribonucleic acid (mRNA) vaccine is allowed
- Patients must not have had prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2gent, or any other immune checkpoint inhibitors
- Patients must not have had prior therapy with PARP inhibitors
- Patients must not have had a prior diagnosis of immunodeficiency or receiving systemicd therapy (defined as >= 10 mg prednisone or equivalent) or any other form ofunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Participants must not be pregnant or nursing due to the possibility of harm to theus or nursing infant from this treatment regimen. Women of childbearing potentialust have a negative urine or serum pregnancy test within 28 days prior togistration. Women/men of reproductive potential must have agreed to use an effectiveve method for the course of the study through 6 months after the last doseudy medication. A woman is considered to be of "reproductive potential" if shehas had menses at any time in the preceding 12 consecutive months. In addition toutine contraceptive methods, "effective contraception" also includes heterosexualbacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancyvention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubalgation. However, if at any point a previously celibate participant chooses to becomeheterosexually active during the time period for use of contraceptive measures, he/sheble for beginning contraceptive measures. Should a woman become pregnant oruspect she is pregnant while she or her partner is participating in this study, shehould inform her treating physician immediately
- Patients must not have a history of (non-infectious) pneumonitis that requiredds or current pneumonitis
- Patients must not have an active infection requiring systemic therapy
- Patients must not have active autoimmune disease that has required systemic treatment2 years (i.e., with use of disease modifying agents, corticosteroids orunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, orhysiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,.) is not considered a form of systemic treatment
Updated on
02 May 2024.
Study ID: NCI-2020-06838
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