Sorafenib Tosylate With or Without Everolimus in Treating Patients With Localized, Unresectable, or Metastatic Liver Cancer

NCT01005199 | Completed Phase 2

• 6 other identifiers: SAKK 77/08 and SASL 29SWS-SAKK-77/08SWS-SASL-292009-011884-35EU-20983CDR0000657702
• Study Type: interventional
• Target: 106
• Locations: 3 countries
• Sites: 15

Brief Summary

RATIONALE: Sorafenib tosylate and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: This randomized phase II trial is studying giving sorafenib tosylate together with everolimus to see how well it works compared with sorafenib tosylate alone in treating patients with localized, unresectable, or metastatic liver cancer.

Conditions

Liver Cancer

Keywords

adult primary hepatocellular carcinoma; localized unresectable adult primary liver cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  at 12 weeks

Secondary Outcomes (10)

• Objective response

  during trial treatment and follow-up (max. 3 years)

• Disease stabilization (DS)

  under trial treatment

• Duration of disease stabilization

  Duration of DS (CR, PR or SD) will be calculated from the time that measurement criteria are met for the first time until documented tumor progression.

• Progression-free survival (PFS)

  PFS will be calculated from randomization until documented tumor progression or death, whichever occurs first

• Time to progression (TTP)

  TTP will be calculated from randomization until documented tumor progression or tumor-related death

Study Arms (2)

Arm A: Sorafenib standard

EXPERIMENTAL

• Arm A (standard treatment): Sorafenib 2 x 400 mg daily until progressive disease, unacceptable toxicity, or consent withdrawal. (46 patients).

Drug: sorafenib tosylate

Arm B: Sorafenib + everolimus

EXPERIMENTAL

• Arm B (investigational treatment): Sorafenib 2 x 400 mg daily plus everolimus 1 x 5 mg daily until progressive disease, unacceptable toxicity, or consent withdrawal. (60 patients)

Drug: everolimus; Drug: sorafenib tosylate

Interventions

everolimus DRUG

Sorafenib 2 x 400 mg daily plus everolimus 1 x 5 mg daily

Also known as: RAD001

Arm B: Sorafenib + everolimus

sorafenib tosylate DRUG

Sorafenib 2 x 400 mg daily

Also known as: BAY 43-9006

Arm A: Sorafenib standard; Arm B: Sorafenib + everolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (15)

Medizinische Universität Wien

Vienna, 1090, Austria

Location

Szent Laszlo Korhaz

Budapest, 1097, Hungary

Location

Saint Claraspital AG

Basel, CH-4016, Switzerland

Location

Clinical Cancer Research Center at University Hospital Basel

Basel, CH-4031, Switzerland

Location

Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Kantonsspital Bruderholz

Bruderholz, CH-4101, Switzerland

Location

Hopital Cantonal Universitaire de Geneve

Geneva, CH-1211, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Kantonsspital Liestal

Liestal, CH-4410, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

CHCVS - Hôpital de Sion

Sion, 1950, Switzerland

Location

Regionalspital

Thun, 3600, Switzerland

Location

City Hospital Triemli

Zurich, CH-8063, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, CH-8091, Switzerland

Location

Related Publications (1)

• Koeberle D, Dufour JF, Demeter G, Li Q, Ribi K, Samaras P, Saletti P, Roth AD, Horber D, Buehlmann M, Wagner AD, Montemurro M, Lakatos G, Feilchenfeldt J, Peck-Radosavljevic M, Rauch D, Tschanz B, Bodoky G; Swiss Group for Clinical Cancer Research (SAKK). Sorafenib with or without everolimus in patients with advanced hepatocellular carcinoma (HCC): a randomized multicenter, multinational phase II trial (SAKK 77/08 and SASL 29). Ann Oncol. 2016 May;27(5):856-61. doi: 10.1093/annonc/mdw054. Epub 2016 Feb 15.

  PMID: 26884590 RESULT

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular

Interventions

Everolimus; Sorafenib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Dieter Koeberle, MD

  Cantonal Hospital of St. Gallen

  STUDY CHAIR

• Jean-Francois Dufour, MD

  Insel Gruppe AG, University Hospital Bern

  STUDY CHAIR

• Gyorgy Bodoky, MD, PhD

  Szent Laszlo Korhaz

  STUDY CHAIR

• Michael Montemurro, MD

  CHUV Lausanne

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2009
• First Posted: October 30, 2009
• Study Start: November 1, 2009
• Primary Completion: June 1, 2013
• Study Completion: March 1, 2016
• Last Updated: May 15, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); HU (1); CH (13)