Back to results

Sorafenib Tosylate With or Without Pravastatin in Treating Patients With Liver Cancer and Cirrhosis

Primary Purpose

Liver Cancer

Status

Completed

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

pravastatin sodium

sorafenib tosylate

About this trial

This is an interventional treatment trial for Liver Cancer focused on measuring adult primary hepatocellular carcinoma, localized unresectable adult primary liver cancer, advanced adult primary liver cancer, recurrent adult primary liver cancer

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Hopital Du Bocage

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

sorafenib

sorafenib + pravastatine

Arm Description

sorafenib

sorafenib + pravastatine

Outcomes

Primary Outcome Measures

Overall survival

Secondary Outcome Measures

Progression-free survival

Time to progression

Full Information

NCT ID

NCT01075555

First Posted

February 24, 2010

Last Updated

March 27, 2020

Sponsor

Federation Francophone de Cancerologie Digestive

Collaborators

Centre Hospitalier Universitaire Dijon

1. Study Identification

Unique Protocol Identification Number

NCT01075555

Brief Title

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

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Completed

Study Start Date

February 2010 (undefined)

Primary Completion Date

September 2015 (Actual)

Study Completion Date

September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Federation Francophone de Cancerologie Digestive

Collaborators

Centre Hospitalier Universitaire Dijon

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Liver Cancer

Keywords

adult primary hepatocellular carcinoma, localized unresectable adult primary liver cancer, advanced adult primary liver cancer, recurrent adult primary liver cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

323 (Actual)

8. Arms, Groups, and Interventions

Arm Title

sorafenib

Arm Type

Active Comparator

Arm Description

sorafenib

Arm Title

sorafenib + pravastatine

Arm Type

Experimental

Arm Description

sorafenib + pravastatine

Intervention Type

Drug

Intervention Name(s)

pravastatin sodium

Intervention Type

Drug

Intervention Name(s)

sorafenib tosylate

Primary Outcome Measure Information:

Title

Overall survival

Time Frame

2014

Secondary Outcome Measure Information:

Title

Progression-free survival

Time Frame

2014

Title

Time to progression

Time Frame

2014

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jean-Louis Jouve

Organizational Affiliation

Hopital Du Bocage

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Jacques Denis, MD

Organizational Affiliation

Hopital Louise Michel

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hopital Du Bocage

City

Dijon

ZIP/Postal Code

21000

Country

France

12. IPD Sharing Statement

Citations:

PubMed Identifier

31125576

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.

Results Reference

background

Learn more about this trial

Sorafenib Tosylate With or Without Pravastatin in Treating Patients With Liver Cancer and Cirrhosis

We'll reach out to this number within 24 hrs