Know Cancer

or
forgot password

A Phase I Open Label/Phase II Randomized, Double-Blind, Multicenter Trial Investigating the Combination of Everolimus and TransArterial ChemoEmbolization (TACE) With Doxorubicin in Patients With Hepatocellular Carcinoma


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Liver Cancer

Thank you

Trial Information

A Phase I Open Label/Phase II Randomized, Double-Blind, Multicenter Trial Investigating the Combination of Everolimus and TransArterial ChemoEmbolization (TACE) With Doxorubicin in Patients With Hepatocellular Carcinoma


OBJECTIVES:

- Determine the recommended dose of everolimus in patients with hepatocellular carcinoma
(HCC) treated with transarterial chemoembolization with doxorubicin-eluting beads
(TACE). (Phase I)

- Determine the efficacy and tolerability of everolimus in patients with HCC treated with
TACE as compared to TACE alone. (Phase II)

OUTLINE: This is a multicenter, dose-escalation phase I study followed by a randomized phase
II study.

- Phase I: Patients receive oral everolimus once daily in the absence of disease
progression or unacceptable toxicity. Beginning 7 days after the start of everolimus
patients undergo transarterial chemoembolization (TACE) comprising doxorubicin-eluting
beads into the hepatic artery followed in 4 weeks by an MRI. If viable tumor is found
patients undergo another TACE treatment continuing every 4 weeks for up to 5
treatments.

- Phase II: Patients are stratified according to center, age (≤ 60 vs > 60 years), and
number of lesions (≤ 3 vs > 3). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive oral placebo once daily for up to 12 months and undergo
TACE comprising doxorubicin-eluting beads as in phase I at the maximum tolerated
dose (MTD).

- Arm II: 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.

In both arms, patients receive treatment for up to 12 months in the absence of disease
progression or unacceptable toxicity.

Blood samples are collected periodically for analysis of AFP tumor markers. Patients also
complete quality of life questionnaires, Health Economic Assessment, and EQ5D questionnaires
at baseline and periodically during the study.

After completion of study treatment, patients are followed on day 30, and then every 3
months.

Inclusion Criteria


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)

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

Dose-limiting toxicity (Phase I)

Outcome Description:

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

Outcome Time Frame:

after 6 weeks from registration

Safety Issue:

Yes

Principal Investigator

Jean-Francois Dufour, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University Hospital Inselspital, Berne

Authority:

Switzerland: Swissmedic

Study ID:

SAKK 77/09

NCT ID:

NCT01009801

Start Date:

February 2010

Completion Date:

September 2013

Related Keywords:

  • Liver Cancer
  • adult primary hepatocellular carcinoma
  • recurrent adult primary liver cancer
  • localized resectable adult primary liver cancer
  • Liver Neoplasms
  • Carcinoma, Hepatocellular

Name

Location