Clinical trial NCT02383433 (phase 2, status: terminated)
Conditions: metastatic pancreatic adenocarcinoma
ICD codes: C22.0, C22.1, C4A.9, C7B.1, D09.9, C4A.0, C4A.31
Drugs: regorafenib, gemcitabine hydrochloride
SMILES: [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1, NC1=NC(=O)N(C=C1)[C@@H]1O[C@H](CO)[C@@H](O)C1(F)F
Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed metastatic pancreatic
             adenocarcinoma (or any mixed pathology if adenocarcinoma is predominant)

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded) as >
             20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT)
             scan

          -  Prior Therapies: Patients must have received at least one prior systemic chemotherapy
             regimen for metastatic pancreatic cancer. They should have experienced disease
             progression or intolerable toxicity from that regimen.

          -  Patients who have received prior non-gemcitabine-based systemic chemotherapy for
             metastatic disease at any time 4 weeks prior to enrollment, or those who are beyond 12
             months of exposure to gemcitabine-based chemotherapy regimen are allowed.

          -  Prior chemotherapy, radiation therapy, concurrent chemoradiation are allowed if used
             for treatment of non-metastatic disease.

          -  Any chemotherapy must have been completed 4 weeks prior to enrollment

          -  Any radiotherapy must have been completed 2 weeks prior to enrollment

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Life expectancy of at least 12 weeks (3 months)

          -  Subjects must be able to understand and be willing to sign the written informed
             consent form; a signed informed consent form must be appropriately obtained prior to
             the conduct of any trial-specific procedure

          -  All acute toxic effects of any prior treatment have resolved to National Cancer
             Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version (v)4.0
             grade 1 or less at the time of signing the informed consent form (ICF)

          -  Total bilirubin =< 1.5 x the upper limits of normal (ULN)

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (=< 5
             x ULN for subjects with liver involvement of their cancer)

          -  Alkaline phosphatase limit =< 2.5 x ULN (=< 5 x ULN for subjects with liver
             involvement of their cancer)

          -  Lipase =< 1.5 x the ULN

          -  Serum creatinine =< 1.5 x the ULN

          -  International normalized ratio (INR)/partial thromboplastin time (PTT) 1.5 x ULN;
             (subjects who are therapeutically treated with an agent such as warfarin or heparin
             will be allowed to participate provided that no prior evidence of underlying
             abnormality in coagulation parameters exists; close monitoring of at least weekly
             evaluations will be performed until INR/PTT is stable based on a measurement that is
             pre-dose as defined by the local standard of care)

          -  Platelet count >= 100000/mm^3, hemoglobin (Hb) ≥ 9 g/dL, absolute neutrophil count
             (ANC) ≥ 1500/mm^3; blood transfusion to meet the inclusion criteria will not be
             allowed

          -  Women of childbearing potential must have a negative serum pregnancy test performed
             within 7 days prior to the start of study drug; post-menopausal women (defined as no
             menses for at least 1 year) and surgically sterilized women are not required to
             undergo a pregnancy test

          -  Subjects (men and women) of childbearing potential must agree to use adequate
             contraception beginning at the signing of the ICF until at least 3 months after the
             last dose of study drug; the definition of adequate contraception will be based on the
             judgment of the principal investigator or a designated associate

          -  Subject must be able to swallow and retain oral medication

        Exclusion Criteria:

          -  Chemotherapy within 4 weeks prior to entering the study, radiotherapy within 2 weeks
             prior to entering the study or failure to recover from adverse events to grade 1 or
             less due to agents administered more than 4 weeks earlier

          -  Use of any other investigational agents

          -  Previous assignment to treatment during this study; subjects permanently withdrawn
             from study participation will not be allowed to re-enter study

          -  Uncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm
             Hg [NCI-CTCAE v4.0] on repeated measurement) despite optimal medical management

          -  Active or clinically significant cardiac disease including:

               -  Congestive heart failure - New York Heart Association (NYHA) > class II

               -  Active coronary artery disease

               -  Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or
                  digoxin

               -  Unstable angina (anginal symptoms at rest), new-onset angina within 3 months
                  before randomization, or myocardial infarction within 6 months before
                  randomization

          -  Evidence or history of bleeding diathesis or coagulopathy

          -  Any hemorrhage or bleeding event >= NCI CTCAE grade 3 within 4 weeks prior to start of
             study medication

          -  Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular
             accident (including transient ischemic attacks) deep vein thrombosis or pulmonary
             embolism within 6 months of informed consent

          -  Subjects with any previously untreated or concurrent cancer that is distinct in
             primary site or histology from pancreatic cancer except cervical cancer in-situ,
             treated basal cell carcinoma, or superficial bladder tumor; subjects surviving a
             cancer that was curatively treated and without evidence of disease for more than 3
             years before randomization are allowed; all cancer treatments must be completed at
             least 3 years prior to study entry (i.e., signature date of the informed consent form)

          -  Patients with phaeochromocytoma

          -  Known history of human immunodeficiency virus (HIV) infection or current chronic or
             active hepatitis B or C infection requiring treatment with antiviral therapy

          -  Any infection requiring ongoing intravenous antibiotics for management

          -  Symptomatic metastatic brain or meningeal tumors; treated and stable, asymptomatic
             brain metastases, as long as treatment was greater than 4 weeks prior to informed
             consent, are allowed

          -  Presence of a non-healing wound, non-healing ulcer, or bone fracture

          -  Renal failure requiring hemo-or peritoneal dialysis

          -  Dehydration grade >= 1 NCI-CTCAE v4.0

          -  Patients with seizure disorder requiring medication

          -  Persistent proteinuria >= grade 3 NCI-CTCAE v4.0 (> 3.5 g/24 hrs, measured by urine
             protein:creatinine ratio on a random urine sample)

          -  Interstitial lung disease with ongoing signs and symptoms at the time of informed
             consent

          -  Pleural effusion or ascites that causes respiratory compromise (>= NCI-CTCAE version
             4.0 grade 2 dyspnea)

          -  History of organ allograft (including corneal transplant)

          -  Known or suspected allergy or hypersensitivity to any of the study drugs, study drug
             classes, or excipients of the formulations given during the course of this trial

          -  Any malabsorption condition

          -  Women who are pregnant or breast-feeding

          -  Any condition which, in the investigator's opinion, makes the subject unsuitable for
             trial participation

          -  Substance abuse, medical, psychological or social conditions that may interfere with
             the subject's participation in the study or evaluation of the study results