Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
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.
Phase
Phase 2
Funding Agency/Sponsor
National Cooperative Group
Disease
Pancreatic, Liver, and Related Cancers
Enrollment Eligibility
Inclusion Criteria:
- STEP 0 (PRE-REGISTRATION) INCLUSION CRITERIA
- Patient must be >= 18 years of age on day of consent
- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0-2
- Patient must have a diagnosis of pancreatic cancer and have successfully undergone a
curative intent surgical resection and must have no evidence of recurrent disease as
determined by the investigator
- NOTE: This includes patients with adenocarcinoma, acinar carcinoma, squamous cell
carcinoma adenosquamous and variants thereof. Patients with neuroendocrine tumors
are excluded from enrolling
- Patient must (1) be planning to receive, (2) be receiving or (3) have received at
least three combined months (i.e., 12 weeks) of perioperative (neoadjuvant, adjuvant
or a combination of both) systemic, multi-agent chemotherapy. Patients may have had up
to 6 months of perioperative systemic therapy as deemed appropriate by their primary
treating medical team (patients can have received radiation or chemoradiation in
addition to this 6 month course)
- Patient must be no more than 12 weeks from their most recent treatment (this may be
chemotherapy, radiotherapy or surgery)
- Patient must have a known pathogenic or likely pathogenic germline or somatic mutation
in BRCA1, BRCA2, or PALB2, as determined by a Clinical Laboratory Improvement
Amendments (CLIA) certified or equivalently-accredited laboratory. Mutations must be
considered pathogenic or likely pathogenic by a reference database such as ClinVar or
OncoKb.org
- STEP 1 (RANDOMIZATION) INCLUSION CRITERIA
- Patient must have met the eligibility criteria outlined above
- Patient must have undergone at least 3 combined months (i.e., 12 weeks) of
perioperative (neoadjuvant, adjuvant or a combination of both) systemic, multi-agent
chemotherapy. Patients may have had up to 6 months of perioperative systemic therapy
as deemed appropriate by their primary treating medical team (patients can have
received radiation or chemoradiation in addition to this 6 months course)
- Central expert reviewer must have determined the patient eligible for randomization
after review of local genetic testing reports
- If mutation in BRCA1, BRCA2 or PALB2 was identified in tumor tissue and the patient
has not previously undergone germline testing, the patient must agree to undergo
germline testing
- Patient must be >= 21 days (three weeks) from their last treatment (including
chemotherapy radiotherapy or surgery) but =< 84 days (twelve weeks) from their last
treatment at the time of Step 1 randomization. Patients who have received neoadjuvant
and/or adjuvant radiotherapy are eligible
- Patient must have recovered from any adverse events due to prior anti-cancer therapy
(i.e., have no residual toxicities > grade 1 with the exception of alopecia and/or
neuropathy)
- Leukocytes >= 3,000/mcL (obtained =< 28 days prior to Step 1 randomization)
- Absolute neutrophil count >= 1,500/mcL (obtained =< 28 days prior to Step 1
randomization)
- Platelets >= 100,000/mcL (obtained =< 28 days prior to Step 1 randomization)
- Hemoglobin >= 9.0 g/dL with no blood transfusion in the past 28 days (obtained =< 28
days prior to Step 1 randomization)
- Total bilirubin =< 1.5 institutional upper limit of normal (ULN) except in patients
with Gilbert's syndrome. Patients with Gilbert's syndrome may enroll if direct
bilirubin =< 2.5 x ULN of the direct bilirubin (obtained =< 28 days prior to Step 1
randomization)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 institutional ULN (obtained =< 28 days prior to Step 1 randomization)
- Creatinine =< 1.5 institutional ULN OR calculated Cockcroft Gault creatinine clearance
> 50 mL/min/1.73 m^2 (obtained =< 28 days prior to Step 1 randomization)
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
- Patient must have the ability to understand the willingness to sign a written informed
consent document, or have legally authorized representative provide authorization to
participate
Exclusion Criteria:
- STEP 1 (RANDOMIZATION) EXCLUSION CRITERIA
- Patient must have no evidence of recurrent or metastatic pancreatic cancer at the time
of randomization as documented by baseline scans obtained =< 4 weeks prior to Step 1
randomization
- Patient must not have previously had evidence of progressive pancreatic cancer while
receiving platinum-based therapy
- Patient must not be receiving any other investigational agents at the time of Step 1
randomization and while on protocol treatment
- Patient must not have any history of allergic reactions attributed to compounds of
similar chemical or biological composition to olaparib
- Patient must not have any personal history of myelodysplastic syndrome (MDS) or acute
myeloid leukemia (AML). Patients with myelodysplastic syndrome/acute myeloid leukemia
or with features suggestive of MDS/AML.
- Patient must not have any uncontrolled gastrointestinal disorder that would, in the
opinion of the investigator, interfere with the ingestion or absorption of olaparib
- 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)
- Patients must not expect to conceive or father children by using accepted and
effective method(s) of contraception or by abstaining from sexual intercourse for the
duration of their participation in the study and for 6 months after the last dose of
protocol treatment for female patients and for 3 months after the last dose of
protocol treatment for male patients. Patients must also not donate sperm while on
protocol treatment and for 3 months after the last dose of protocol treatment.
Patients must also not breast-feed while on protocol treatment and for 1 month after
the last dose of protocol treatment
- Patient must not have resting electrocardiogram (ECG) indicating uncontrolled,
potentially reversible cardiac conditions, as judged by the investigator (e.g.
unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure,
corrected QT (QTc) prolongation > 500 ms, electrolyte disturbances, etc.) or have
congenital long QT syndrome
- Concomitant use of known potent CYP3A4/5 inhibitors such as ketoconazole,
itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and
nelfinavir is prohibited
- Patients who are being actively treated for an ongoing concurrent malignancy are
ineligible, with the exception of those receiving adjuvant hormone therapies and those
receiving topical therapies for skin cancers
- Patient must not have, in the opinion of the investigator, any other concurrent
medical condition that would prevent the patient from complying with the study
procedures
- Patient must not be considered a poor medical risk due to a serious, uncontrolled
medical disorder, non-malignant systemic disease or active, uncontrolled infection.
Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent
(within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable
spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral
lung disease on high resolution computed tomography (HRCT) scan or any psychiatric
disorder that prohibits obtaining informed consent
- Patient must not have had major surgery within 2 weeks prior to Step 1 randomization
and patients must have recovered from any effects of any major surgery