Inclusion Criteria:
- Ability to understand and the willingness to sign a written informed consent document
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Clinically-confirmed diagnosis of non-metastatic, adenocarcinoma of the pancreas
- At time of screening, must have resectable pancreatic adenocarcinoma (as defined by
institutional guidelines)
- Must be deemed fit to undergo planned curative resection as determined by
institutional standards
- No history of previous chemotherapy
- Based on available imaging, participant must have at least one disease lesion that can
be biopsied in accordance with institutional standards
- Hemoglobin >= 10.0 g/dL with no blood transfusion within 28 days of starting treatment
(at time of registration and within 4 weeks prior to initiating window treatment)
- White blood cells (WBC) > 3 x 10^9/L (at time of registration and within 4 weeks prior
to initiating window treatment)
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (> 1500 per mm^3) (at time of
registration and within 4 weeks prior to initiating window treatment)
- May be waived on a case-by-case basis for patient populations recognized to have
normal baseline values below this level
- Platelet count >= 100 x 10^9/L (> 100,000 per mm^3) (at time of registration and
within 4 weeks prior to initiating window treatment)
- Creatinine =< 1.5 x upper limit of normal (ULN), OR measured or calculated creatinine
clearance (glomerular filtration rate (GFR)) can also be used in place of creatinine
or creatinine clearance (CrCl)) >= 60 mL/min/1.73m^2 for participants with creatinine
levels > 1 x institutional ULN (at time of registration and within 4 weeks prior to
initiating window treatment)
- Creatinine clearance should be calculated per institutional standard. For
participants with a baseline calculated creatinine clearance below normal
institutional laboratory values, a measured baseline creatinine clearance should
be determined. Individuals with higher values felt to be consistent with inborn
errors of metabolism will be considered on a case-by-case basis
- Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN) (at time of
registration and within 4 weeks prior to initiating window treatment)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x
ULN (at time of registration and within 4 weeks prior to initiating window treatment)
- Participants must be willing to undergo one mandatory on-study tumor biopsies prior to
initiating window treatment (i.e., cobimetinib or olaparib)
- Participant is willing and able to comply with the protocol for the duration of the
study including undergoing treatment and scheduled visits and examinations including
follow up
- Participant must be able to swallow tablets or capsules. A participant with any
gastrointestinal disease that would impair ability to swallow, retain, or absorb drug
is not eligible
- Female participants of childbearing potential must have a negative urine or serum
pregnancy test within 72 hours prior to receiving the first dose of study medication.
If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
test will be required
- Female participants of childbearing potential agree to use adequate methods of
contraception starting with the first dose of study therapy through 60 days after the
last dose of study therapy. Participants of childbearing potential are those who have
not been surgically sterilized or have not been free from menses for > 1 year without
an alternative medical cause
- Male participants must agree to use an adequate method of contraception starting with
the first dose of study therapy through 60 days after the last dose of study therapy
- Male patients must use a condom during treatment and for 3 months after the last dose
of olaparib when having sexual intercourse with a pregnant woman or with a woman of
childbearing potential. Female partners of male patients should also use a highly
effective form of contraception if they are of childbearing potential
- No other prior invasive malignancy is allowed except for the following: adequately
treated basal (or squamous cell) skin cancer, in situ breast or cervical cancer. Stage
I or II invasive cancer treated with a curative intent without evidence of disease
recurrence for at least five years
- Individuals must not have known active hepatitis B virus (HBV) or hepatitis C virus
(HCV) infection prior to trial registration. Those who have completed curative therapy
for HCV are eligible. Patients with known human immunodeficiency virus (HIV) infection
are eligible if they meet each of the following 3 criteria:
- CD4 counts >= 350 mm^3
- Serum HIV viral load of < 25,000 IU/ml and
- Treated on a stable antiretroviral regimen
Exclusion Criteria:
- History of previous chemotherapy, or radiation therapy
- Evidence of metastasis to distant organs (liver, peritoneum, lung, others)
- Medical co-morbidities that are deemed to make risk of surgery unacceptably high as
determined by institutional standards
- Recent major surgery within 4 weeks prior to starting study treatment. Minor surgery
within 2 weeks of starting study treatment. Patients must be recovered from effects of
surgery
- Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin,
rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's wort) or
moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil)
- Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin,
clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,
saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g.,
ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil)
- Concomitant use of other anti-cancer therapy (chemotherapy, immunotherapy, hormonal
therapy (hormone replacement therapy is acceptable), radiotherapy (except for
palliative), biological therapy or other novel agent) or live virus and live bacterial
vaccines while the patient is receiving study medication. Strong or moderate CYP3A
inhibitors and inducers should not be taken with study treatment; however, if no other
suitable alternative concomitant medication is available, dose reductions may be
allowed under careful monitoring
- Known severe hypersensitivity to cobimetinib or olaparib (or equivalent agents,
respectively), or any excipient of these medicinal products, or history of allergic
reactions attributed to compounds of similar chemical or biologic composition to
cobimetinib or olaparib
- Clinically significant cardiac disease or impaired cardiac function, including any of
the following:
- Clinically significant and/or uncontrolled heart disease such as congestive heart
failure (New York Heart Association grade >= 2) uncontrolled hypertension, or
clinically significant arrhythmia currently requiring medical treatment
- Corrected QT using Fridericia's formula (QTcF) > 470 msec for females, or > 450
msec for males, on screening electrocardiogram (ECG) or congenital long QT
syndrome
- Acute myocardial infarction or unstable angina pectoris < 6 months prior to
screening
- Psychiatric illness/social situations that would limit compliance with study
requirements
- Participants with a history of hypersensitivity reactions to study agents or their
excipients
- Participant is pregnant or breastfeeding, or expecting to conceive or father children
within the projected duration of the trial, starting with the screening visit through
120 days after the last dose of trial treatment
