Transarterial Chemoembolization With Doxorubicin With or Without Everolimus in Treating Patients With Liver Cancer

NCT01009801 | Terminated Phase 1

• 5 other identifiers: SAKK 77/09SWS-SAKK-77-09SWS-SASL-30EU-20986CDR0000658353
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 8

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Chemoembolization kills tumor cells by carrying drugs directly into the tumor and blocking the blood flow to the tumor. 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. It is not yet known whether transarterial chemoembolization with doxorubicin is more effective when given alone or when given together with everolimus in treating patients with liver cancer. PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of everolimus when given together with transarterial chemoembolization with doxorubicin and to see how well it works compared with giving transarterial chemoembolization with doxorubicin alone in treating patients with liver cancer.

Conditions

Liver Cancer

Keywords

adult primary hepatocellular carcinoma; recurrent adult primary liver cancer; localized resectable adult primary liver cancer

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity (Phase I)

  Dose limiting toxicity (DLT) (observed within the first TACE period)

  after 6 weeks from registration

• Time to progression (Phase II)

  12 weeks after randomisation

Secondary Outcomes (7)

• Time to progression (Phase I)

  12 weeks after registration

• Progression-free survival (Phase II)

  Time from randomization until event occurs (see description):

• Progression-free survival at 12 months (Phase II)

  within 12 months after randomisation

• Tumor response according to adapted RECIST criteria (Phase II)

  during treatment

• Overall survival (Phase II)

  Time from randomisation until death from any cause

Study Arms (2)

Arm I

ACTIVE COMPARATOR

Patients receive oral placebo once daily for up to 12 months and undergo TACE comprising doxorubicin-eluting beads as in phase I at the MTD.

Drug: doxorubicin-eluting beads; Other: placebo

Arm II

EXPERIMENTAL

Patients receive oral everolimus once daily for up to 12 months and undergo TACE comprising doxorubicin-eluting beads as in phase I at the MTD.

Drug: doxorubicin-eluting beads; Drug: everolimus

Interventions

doxorubicin-eluting beads DRUG

Patients receive oral placebo or everolimus once daily for up to 12 months and undergo TACE comprising doxorubicin-eluting beads as in phase I at the MTD.

Also known as: Adriamycin

Arm I; Arm II

everolimus DRUG

Patients receive oral everolimus once daily for up to 12 months and undergo TACE comprising doxorubicin-eluting beads as in phase I at the MTD.

Also known as: RAD001

Arm II

placebo OTHER

Patients receive oral placebo once daily for up to 12 months and undergo TACE comprising doxorubicin-eluting beads as in phase I at the MTD.

Arm I

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 * Intermediate stage B (according to Barcelona Clinic Liver Cancer classification) * Child-Pugh score \< 8 * No tumor involvement \> 50% of whole liver * No advanced stage disease (i.e., either portal invasion \[segmental portal obstruction\] or extrahepatic spread) * No presence or history of metastatic disease * Candidate for transarterial chemoembolization after multidisciplinary discussion (tumor board) * Not on an active waiting list for liver transplantation PATIENT CHARACTERISTICS: * WHO performance status 0-1 * Hemoglobin ≥ 90 g/L * Absolute neutrophil count ≥ 1.5 x 10\^9/L * Platelet count ≥ 100 x 10\^9/L * Bilirubin ≤ 1.5 x upper limit of normal (ULN) * ALT ≤ 4 x ULN * INR ≤ 2 * Creatinine ≤ 1.5 x ULN * Not pregnant or nursing * Fertile patients must use effective contraception during and for 12 months after completion of study therapy * Negative pregnancy test * None of the following contraindications: * Complete portal vein thrombosis * Large arterio-portal or arterio-venous fistula within the liver * Allergy to contrast media * Contraindication to hepatic artery catheterization, such as severe peripheral vascular disease precluding catheterization * No active heart disease, including any of the following: * NYHA class II-IV congestive heart failure * Active coronary artery disease (myocardial infarction \> 6 months prior to trial entry allowed) * Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin permitted) * Uncontrolled hypertension * No hypertension, defined as systolic blood pressure (BP) \> 150 mm Hg or diastolic BP \> 90 mm Hg despite optimal medical management * No thrombotic or embolic events within the past 6 months including any of the following: * Cerebrovascular accident (including transient ischemic attacks) * Pulmonary embolism * Deep vein thrombosis * No serious non-healing wounds, including wounds healing by secondary intention, acute or non-healing ulcers, or bone fractures within 3 months of fracture * No evidence of bleeding diathesis * No history of hemoptysis * No clinically serious infection \> grade 2 (NCI CTCAE Version 3.0) except for HBV and HCV infection * No known HIV infection * No CTCAE acute adverse events grade \> 2 after prior TACE therapy * No other prior or concurrent malignancy that is distinct in primary site or histology from HCC, except carcinoma in situ of the cervix, treated nonmelanoma skin cancer, superficial bladder tumor (Ta, Tis, T1), or any cancer curatively treated \> 3 years prior to entry * No psychiatric disorder precluding understanding of information on trial related topics, giving informed consent, filling out QL forms, or interfering with compliance for oral drug intake * No serious underlying medical condition, at the judgment of the investigator, which could impair the ability of the patient to participate in the trial (e.g., active autoimmune disease, uncontrolled diabetes) * No known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs * No contraindication to have MRI (e.g., pacemaker) * No organ allograft * No known impairment of swallowing that would preclude administration of everolimus * Completed baseline quality of life, BL-HEA, and EQ5D questionnaires (Phase II only) * Able to comply and have geographic proximity to allow proper staging and follow-up PRIOR CONCURRENT THERAPY: * At least 4 weeks since prior transarterial embolization/chemoembolization \[limited to 5 treatments\], radiofrequency ablation, cryoablation, radiation therapy or percutaneous ethanol injection * At least 4 weeks since prior sorafenib * At least 30 days since treatment with other experimental drugs or other anticancer therapy, or treatment in another clinical trial * At least 30 days since use of biologic response modifiers (e.g., G-CSF and other hematopoietic growth factors) * More than 4 weeks since prior and no concurrent major surgery * More than 3 weeks since prior and no concurrent radiotherapy * Concurrent erythropoietin allowed provided no dose adjustment is undertaken within 1 month prior to the trial or during the trial * No concurrent anticancer drugs (e.g., bevacizumab, and any drugs that target VEGF or VEGF receptors) * No concurrent investigational drugs * No concurrent known strong CYP3A4 inhibitors (e.g., ketoconazole, fluconazole, itraconazole, voriconazole, erythromycin, clarithromycin, diltiazem, verapamil, and protease inhibitors) * No concurrent known strong CYP3A4 inducers (e.g., carbamazepine, continuous treatment with dexamethasone \[\> 2 mg/day for \> 7 days\], phenobarbital, phenytoin, rifampicin, and St. John's wort) * No concurrent grapefruit, grapefruit juice, and products containing bitter oranges * No concurrent systemic corticosteroids (e.g., \> 1 mg/kg prednisolone) for more than 2 weeks * No concurrent angiotensin 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 (8)

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Kantonsspital Graubuenden

Chur, 7000, Switzerland

Location

Hopital Cantonal Universitaire de Geneve

Geneva, CH-1211, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Clinica Luganese di Moncucco

Lugano, 6903, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Institut Central des Hopitaux Valaisans / Hôpital de Sion

Sion, CH-1951, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, CH-8091, Switzerland

Location

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular

Interventions

Doxorubicin; Everolimus

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)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Sirolimus; Macrolides; Lactones

Study Officials

• Jean-Francois Dufour, MD

  Insel Gruppe AG, University Hospital Bern

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2009
• First Posted: November 9, 2009
• Study Start: February 1, 2010
• Primary Completion: November 1, 2011
• Study Completion: June 1, 2015
• Last Updated: July 7, 2015

Record last verified: 2015-07

Locations

CH (8)