University of Kansas Medical Center

Conditions

• Pancreatic Acinar Cell Carcinoma
• Pancreatic Adenosquamous Carcinoma
• Pancreatic Squamous Cell Carcinoma
• Resectable Pancreatic Acinar Cell Carcinoma
• Resectable Pancreatic Adenocarcinoma
• Resectable Pancreatic Adenosquamous Carcinoma
• Resectable Pancreatic Carcinoma

Eligibility

Eligible Ages

Over 18 Years

Eligible Genders

All

Accepts Healthy Volunteers

No

Criteria

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 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 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)

- 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

- 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 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 have the ability to understand and the willingness to sign a written
informed consent document, or have legally authorized representative provide
authorization to participate

- 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

Recruiting Locations

Study Contact

Detailed Description

PRIMARY OBJECTIVE: I. To determine the relapse-free survival (RFS)-benefit from the addition of a maintenance olaparib following completion of chemotherapy in patients with resected pancreatic carcinoma and a pathogenic germline or somatic mutation in BRCA1, BRCA2 or PALB2. SECONDARY OBJECTIVES: I. To evaluate RFS in patients with olaparib after perioperative chemotherapy compared to those treated with perioperative therapy alone among patients who received prior platinum-based perioperative chemotherapy. II. To evaluate overall survival (OS) in patients treated with olaparib after adjuvant chemotherapy compared to those treated with adjuvant treatment alone. III. To analyze the efficacy of olaparib after chemotherapy in patients with a pathogenic germline BRCA or PALB2 mutation compared to those with a somatic mutation. IV. To analyze survival differences between patients who received neoadjuvant or perioperative chemotherapy compared to those who received adjuvant therapy alone. V. To analyze RFS and OS differences in those who received =< 3 months of perioperative platinum chemotherapy compared to those who received > 3 months of perioperative platinum chemotherapy. VI. To analyze RFS and OS differences in those who received any platinum-based perioperative chemotherapy compared to no-platinum based perioperative chemotherapy. EXPLORATORY OBJECTIVES: I. To analyze RFS and OS differences in patients who had R1 versus (vs) R0 resections, lymph node positivity at resection, and/or elevated or rising CA 19-9 or CEA at time of study enrollment in the post-operative setting. II. To analyze RFS and OS differences with those who had resectable disease at diagnosis compared to those who did not. III. To analyze RFS and OS differences in those with gBRCA1 mutations compared to those with gBRCA2 mutations and gPALB2 mutations. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive olaparib orally (PO) twice daily (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 computed tomography (CT) scans or CT/magnetic resonance imaging (MRI) and collection of blood throughout the study. ARM II: 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. After completion of study treatment, patients are followed up at 30 days, every 4 months for year 1, then every 6 months for years 2-10 after randomization.