Clinical trial NCT01075555: Sorafenib Tosylate With or Without Pravastatin in Treating Patients With Liver Cancer and Cirrhosis
Official title: Randomized Phase III Trial Sorafenib-Pravastatin Versus Sorafenib Alone for the Palliative Treatment of Child-Pugh A Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Liver Cancer
Keywords: adult primary hepatocellular carcinoma
localized unresectable adult primary liver cancer
advanced adult primary liver cancer
recurrent adult primary liver cancer
Lead sponsor: Federation Francophone de Cancerologie Digestive
Sponsor class: OTHER
Collaborators: name: Centre Hospitalier Universitaire Dijon
First posted: 2010-02-25
Enrollment: 323
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Sorafenib tosylate and pravastatin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib tosylate may also stop the growth of liver cancer by blocking blood flow to the tumor. It is not yet known whether sorafenib tosylate is more effective when given alone or together with pravastatin in treating patients with liver cancer and cirrhosis.

PURPOSE: This randomized phase III trial is studying sorafenib tosylate given together with pravastatin to see how well it works compared with giving sorafenib tosylate alone in treating patients with liver cancer and cirrhosis.

Detailed description: OBJECTIVES:

Primary

* To evaluate the effects of sorafenib tosylate and pravastatin versus sorafenib tosylate alone on overall survival of patients with hepatocellular carcinoma and Child-Pugh Class A cirrhosis.

Secondary

* To evaluate the effect of this regimen on progression-free survival, time to progression, time to treatment failure, and quality of life (QLQ-C30 and FACT hep) in these patients.
* To evaluate the benefit of on-site monitoring versus the centralized data management monitoring of these patients.
* To characterize polymorphisms to specify the haplotype diversity in these patients.
* To test both diagnostic and prognostic signatures by quantitative RT-PCR to determine if they can predict response to these regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to participating center, Cancer of the Liver Italian Program (CLIP) score (0 vs 1 vs 2-4), WHO performance status (0 vs 1 vs 2), portal vein thrombosis (presence vs absence), and extrahepatic metastases (presence vs absence). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral sorafenib tosylate twice daily on days 1-28 and oral pravastatin once daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive oral sorafenib tosylate twice daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients complete quality-of-life questionnaires (QLQ-C30 and FACT) at baseline and then every 4 weeks during and after completion of study therapy.

Blood and tissue samples may be collected for laboratory analysis, including pharmacogenomic studies.

After completion of study therapy, patients are followed up periodically.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of hepatocellular carcinoma (HCC), meeting 1 of the following criteria:

  * Histologically confirmed HCC
  * If histological proof can not be obtained (e.g., ascites, coagulation disorders), the diagnosis may be made in cases of cirrhosis according to the 2005 EASL/AASLD criteria by demonstration of a focal hepatic lesion \> 10 mm, meeting 1 of the following criteria:

    * Hypervascular tumor \< 2 cm by 2 dynamic-imaging techniques (e.g., spiral CT scan, MRI scan, or ultrasound with contrast medium)
    * Hypervascular tumor ≥ 2 cm by 1 dynamic-imaging technique (e.g., spiral CT scan, MRI scan, or ultrasound with contrast medium)
* No progressive disease following prior treatment
* Not eligible for curative treatment (i.e., transplantation, resection, or percutaneous destruction) or chemoembolization
* Cancer of the Liver Italian Program (CLIP) prognosis score 0 to 4
* Child-Pugh score A
* No extrahepatic disease threatening the short- or medium-term vital prognosis

PATIENT CHARACTERISTICS:

* WHO performance status 0-2
* Life expectancy \> 12 weeks
* Transaminases ≤ 5 times upper limit of normal (ULN)
* Serum creatinine ≤ 1.5 times ULN
* Not pregnant or nursing
* Fertile patients must use effective contraception during and for 3 months after completion of study therapy
* No other cancerous pathology, except for carcinoma in situ of the cervix, superficial bladder tumors, treated basal cell carcinoma, or any other cancer treated curatively ≥ 3 years ago
* No cardiac insufficiency (NYHA class II or IV congestive heart failure), arterial hypertension, uncontrolled arrhythmia, or myocardial infarction within the past 6 months
* No digestive hemorrhage within the past month
* No major bleeding disorder

PRIOR CONCURRENT THERAPY:

* No prior or other concurrent statins
* No prior sorafenib tosylate

Primary outcomes:
measure: Overall survival
timeFrame: 2014
Secondary outcomes:
measure: Progression-free survival
timeFrame: 2014
measure: Time to progression
timeFrame: 2014
Other outcomes:
Locations:
city: Dijon
country: France
facility: Hopital Du Bocage
Study officials:
affiliation: Hopital Du Bocage
name: Jean-Louis Jouve
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Louise Michel
name: Jacques Denis, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jouve JL, Lecomte T, Bouche O, Barbier E, Khemissa Akouz F, Riachi G, Nguyen Khac E, Ollivier-Hourmand I, Debette-Gratien M, Faroux R, Villing AL, Vergniol J, Ramee JF, Bronowicki JP, Seitz JF, Legoux JL, Denis J, Manfredi S, Phelip JM; PRODIGE-11 investigators/collaborators. Pravastatin combination with sorafenib does not improve survival in advanced hepatocellular carcinoma. J Hepatol. 2019 Sep;71(3):516-522. doi: 10.1016/j.jhep.2019.04.021. Epub 2019 May 22.