Clinical trial NCT01005199 (phase 2, status: completed)
Conditions: liver cancer
ICD codes: D13.4, Z85.05, C22.8, C78.7, C22.9, D37.6
Drugs: everolimus, sorafenib tosylate
SMILES: [H][C@@]1(C[C@@H](C)[C@]2([H])CC(=O)[C@H](C)\C=C(C)\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\C=C\C=C\C=C(C)\[C@H](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](OCCO)[C@@H](C1)OC, CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1
Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically, cytologically, or radiologically confirmed hepatocellular carcinoma
             (HCC)

               -  Localized, unresectable, or metastatic disease

               -  Child-Pugh class A or mildly decompensated Child-Pugh class B liver dysfunction
                  (Child-Pugh score ≤ 7)

               -  Stage B or C disease according to the Barcelona Clinic Liver Cancer (BCLC)
                  staging classification

          -  Measurable disease

               -  At least 1 unidimensionally measurable site of disease (≥ 10 mm in case of a
                  non-nodal lesion or with a short axis ≥ 15 mm in case of a lymph node) by
                  spiral/multi-slice CT/MRI scan according to revised RECIST criteria

          -  No locally advanced disease AND a candidate for radical surgery

          -  No known fibrolamellar HCC or mixed cholangiocarcinoma/HCC

          -  No clinical symptoms or history of CNS metastases or leptomeningeal disease (no
             imaging required)

        PATIENT CHARACTERISTICS:

          -  WHO performance status 0-1

          -  Hemoglobin ≥ 90 g/L

          -  Neutrophil count ≥ 1.5 x 10^9/L

          -  Platelet count ≥ 75 x 10^9/L

          -  Creatinine clearance ≥ 40 mL/min

          -  ALT ≤ 5 times upper limit of normal

          -  INR ≤ 2

          -  Urine dipstick for proteinuria ≤ 1+ OR protein spot urine < 0.6 g/L

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for 12 months after
             completion of study therapy

          -  No prior malignancy within the past 5 years except adequately treated carcinoma in
             situ of the cervix or localized nonmelanoma skin cancer

          -  No history of hemorrhagic or thrombotic cerebrovascular event within the past 12
             months

          -  No documented variceal hemorrhage within the past 3 months

          -  No requirement for anticoagulant therapy except for low-dose anticoagulants for
             maintenance of patency of central venous access or prevention of deep vein thrombosis

          -  No history or presence of clinically significant acute or unstable cardiovascular,
             cerebrovascular, renal, gastrointestinal, pulmonary, endocrine, central nervous
             system, or immunological disorders (except for the presence of hepatitis B or C virus
             or cirrhosis) within the past 6 months

          -  No encephalopathy

          -  No known HIV infection

          -  No active infection requiring IV antibiotics

          -  No arterial hypertension ≥ 150/100 mm Hg despite therapy

          -  No ongoing cardiac dysrhythmias of NCI CTCAE grade ≥ 2, atrial fibrillation of any
             grade, prolongation of QTc > 500 msec on screening electrocardiogram (ECG), or history
             of familial long QT syndrome

          -  No repeated paracentesis (more than 1 per month)

          -  No psychiatric disorder precluding understanding of information of trial-related
             topics, giving informed consent, or interfering with compliance for oral drug intake

          -  No concurrent grapefruit, grapefruit juice, or products containing bitter oranges

          -  Able to take oral medications

          -  Completed baseline quality of life questionnaire

          -  Must be compliant and geographically proximal for follow-up

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  No prior systemic anticancer treatment for this disease

               -  The following prior therapies are allowed provided previously treated lesions
                  remain separate from those to be measured in the current trial and prior
                  treatment is completed within the past 4 weeks

                    -  Surgery

                    -  Liver-directed therapy (e.g., transarterial embolization/chemoembolization
                       [limited to 5 treatments], radiofrequency ablation, cryoablation,
                       radiotherapy, or percutaneous ethanol injection)

          -  No prior organ transplantation

          -  No concurrent estrogen-containing supplementary therapy

          -  No concurrent full-dose anticoagulation with coumarin derivatives

          -  No concurrent elective major surgery

          -  No concurrent radiotherapy (concurrent analgesic radiotherapy of non-target lesions
             allowed)

          -  No concurrent or anticipated need for CYP3A4 inhibitors or inducers, unless the drugs
             are medically necessary and no substitutes are available, including any of the
             following:

               -  Ketoconazole

               -  Itraconazole

               -  Voriconazole

               -  Erythromycin

               -  Clarithromycin

               -  Diltiazem

               -  Verapamil

               -  Protease inhibitors

          -  No concurrent strong CYP3A4 inducers*, including any of the following:

               -  Carbamazepine

               -  Continuous dexamethasone (> 2 mg/day for > 7 days)

               -  Phenobarbital

               -  Phenytoin

               -  Rifampicin

               -  St. John's wort NOTE: *Concurrent antacids allowed provided they are administered
                  > 1 hour before or > 1 hour after trial drug administration.

          -  No other concurrent experimental drugs or anticancer therapy or treatment in another
             clinical trial within the past 30 days

          -  No other concurrent investigational drugs

          -  No chronic systemic steroids or other immunosuppressive agents

          -  No concurrent angiotension converting enzyme inhibitors (ACE-I)