| Eligibility |
Inclusion Criteria:
1. Ability to understand and the willingness to sign a written informed consent.
2. Patients must have histologically or cytologically confirmed recurrent or metastatic
pancreatic adenocarcinoma.
3. No prior systemic therapy for metastatic or recurrent disease.
- Prior adjuvant therapy, if completed more than 6 months prior to date of
enrollment, is acceptable.
- Radiosensitizing chemotherapy, if completed at least 4 weeks from date of
enrollment, is acceptable.
4. Measurable disease per RECIST1.1 criteria
5. Age 18-70 years at the time of enrollment
6. ECOG performance status 0 or 1
7. Have resolution of toxic effect(s) or intervention complication to Grade 1 or less
(except alopecia) from any prior chemotherapy, major surgery, or radiation therapy of
>30 Gy.
8. Adequate hematologic, hepatic, and renal function. All screening labs should be
performed within 14 days of enrollment date.
- Hemoglobin = 10 g/dL
- ANC = 1,500/µL
- Platelets = 100,000/µL
- Total bilirubin < 1.5 x institutional ULN
- AST (SGOT) & ALT(SGPT)= 2.5 x institutional ULN in patients without known liver
metastasis; = 5 x institutional ULN in patients with known liver metastasis
- Serum creatinine = 1.5 times ULN, and calculated creatinine clearance = 60 mL/min
using the Cockcroft-Gault equation)
- INR or PT International Normalized Ratio (INR) or Prothrombin Time (PT) =1.5
times the ULN
- Albumin = 3.0 g/dL
9. Female patients of childbearing potential must have a negative pregnancy test (either
urine or serum pregnancy test). If the urine pregnancy test is positive or cannot be
confirmed as negative, a serum pregnancy test will be required. A female of
child-bearing potential is any woman (regardless of sexual orientation, having
undergone a tubal ligation, or remaining celibate by choice) who meets the following
criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e.,
has had menses at any time in the preceding 12 consecutive months).
10. Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 120 days following completion of therapy.
Should a woman become pregnant or suspect she is pregnant while participating in this
study, she should inform her treating physician, or study team member, immediately.
Exclusion Criteria:
1. Is currently participating and receiving study therapy in a first line setting for
metastatic or recurrent pancreatic adenocarcinoma.
2. Participated in a study of an investigational agent or used an investigational device
within 4 weeks of the first dose of study treatment.
3. Patients with known untreated brain metastases. Patients without known or suspected
brain metastases do not require radiologic imaging prior to enrollment.
4. Has a known additional malignancy that is progressing or requires active treatment.
Note: Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of
the skin that has undergone potentially curative therapy or in situ cervical cancer.
5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, significant pulmonary disease (shortness of breath at rest or mild
exertion), or uncontrolled infection or psychiatric illness/social situations that
would limit compliance with study requirements.
6. History of the following cardiac conditions:
7. Congestive cardiac failure of >Grade II severity according to the NYHA (defined as
symptomatic at less than ordinary levels of activity);
8. Ischemic cardiac event including myocardial infarction within 3 months prior to date
of enrollment
9. Uncontrolled cardiac disease, including unstable angina pectoris, uncontrolled
hypertension (i.e. sustained systolic BP >160 mmHg or diastolic BP >90 mmHg), cardiac
arrhythmia, or need to change medication due to lack of disease control within 6 weeks
prior to date of enrollment;
10. History or presence of sustained bradycardia (=55 BPM), left bundle branch block,
cardiac pacemaker or ventricular arrhythmia. Note: Patients with a supraventricular
arrhythmia requiring medical treatment, but with a normal ventricular rate are
eligible;
11. Known family history or personal history of long QTc syndrome or previous drug-induced
QTc prolongation of at least Grade 3 (QTc >500 ms).
12. Abnormal left ventricular ejection fraction (LVEF) on ECHO or MUGA less than <45%.
13. Current treatment with any agent known to cause Torsades de Pointes which cannot be
discontinued at least five half-lives or two weeks prior to the first dose of study
treatment.
14. Screening 12-lead ECG, in triplicate, with a measurable QTc interval according to
Fridericia's correction >450 ms.
15. Known active infection with human immunodeficiency virus (HIV), hepatitis B or C
viruses (screening not required, follow institutional practice):
16. Patients who have a history of hepatitis B infection are eligible provided they are
hepatitis B surface antigen negative.
17. Patients who have a history of hepatitis C infection are eligible provided they have
no evidence of hepatitis C ribonucleic acid using a quantitative polymerase chain
reaction assay at least 6 months after completing treatment for hepatitis C infection.
18. Active, clinically significant serious infection requiring treatment with antibiotics,
anti-virals or anti-fungals.
19. Treatment with any medication which is predominantly metabolized by CYP3A4 and has a
narrow therapeutic index
20. Major surgery within 4 weeks prior to date of enrollment; excluding skin biopsies and
procedures for insertion of central venous access devices.
21. Inability to tolerate oral medication
22. Existing gastrointestinal disease affecting drug absorption such as celiac disease or
Crohn's disease, or previous bowel resection which is considered to be clinically
significant or could interfere with absorption.
23. Known lactose intolerance
24. Is pregnant or breastfeeding
25. Any significant medical condition lab abnormality, or psychiatric illness, in the
opinion of the investigator, that might interfere with the patient's participation in
the study or in the evaluation of the study results.
26. Unwillingness or inability to comply with study procedures.
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