Liver Cancer
Conditions
Keywords
adult primary hepatocellular carcinoma, localized unresectable adult primary liver cancer, advanced adult primary liver cancer
Brief summary
RATIONALE: Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping anticancer drugs near the tumor. Sunitinib malate 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 chemoembolization is more effective with or without sunitinib malate in treating patients with liver cancer. PURPOSE: This randomized phase II/III trial is studying the side effects of chemoembolization of the liver and to see how well in works when given together with or without sunitinib malate in treating patients with liver cancer.
Detailed description
OBJECTIVES: Primary * To evaluate unacceptable bleeding or hepatic failure at 10 weeks post-treatment in patients with unresectable hepatocellular carcinoma treated with transarterial chemoembolization in combination with sunitinib malate versus transarterial chemoembolization alone. * To evaluate the overall survival of these patients. Secondary * To evaluate the tumor stabilization rate in these patients. * To evaluate the safety of this regimen in these patients. * To evaluate the disease-free survival of these patients. * To evaluate the relapse-free survival of these patients. * To evaluate the quality of life of these patients. * To evaluate the overall survival rate at 2 years of these patients. OUTLINE: This is a multicenter study. Pilot: Patients receive oral sunitinib malate once daily on days 1-28. Beginning 7-10 days later, patients undergo 1-3 courses of transarterial chemoembolization (TACE). Treatment repeats every 6 weeks for 1 year. Randomization: Patients are stratified according to main tumor diameter (\< 5 cm vs ≥ 5 cm), nodular involvement (uninodular vs multinodular), and center. Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive sunitinib malate and TACE as in the pilot phase. * Arm II: Patients receive oral placebo once daily on days 1-28 and TACE as in the pilot phase. Quality of life is assessed periodically.
Interventions
DRUGsunitinib malate
placebo 3cps/days 4 weeks over 6 during 1 year
DRUGPlacebo
placebo 3cps/days 4 weeks over 6 during 1 year
PROCEDUREtransarterial chemoembolization
Chimioembolisation
Sponsors
Federation Francophone de Cancerologie Digestive
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed hepatocellular carcinoma or liver tumor responding to the Barcelona criteria * Child-Pugh score of 5-6 (Class A) * Tumor suitable for transarterial chemoembolization (one or more planned courses allowed) * Tumor not suitable for surgical resection * No extrahepatic metastases, including cerebral metastases PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Absolute neutrophil count ≥ 1.5 x 10\^9/L * Platelet count ≥ 100 x 10\^9/L * Hemoglobin ≥ 10 g/dL * PT ≥ 50% * Creatinine ≤ 120 μmol/L * Bilirubin normal * ALT/AST ≤ 3.5 times upper limit of normal (ULN) * Alkaline phosphatases ≤ 4 times ULN * Fibrinogen ≥ 1.5 g/L * Not pregnant or nursing * Fertile patients must use effective contraception * No portal vein thrombosis * Able to comply with scheduled follow-up and management of toxicity * No uncontrolled hypertension or requiring ≥ 2 classes of antihypertensive drugs * No concomitant disease or uncontrolled severe disease * No contraindications to the vascular occlusion procedure * No prior or concurrent malignancy within the past 5 years, except adequately treated cone-biopsied carcinoma in situ of the cervix or basal cell carcinoma of the skin * No psychiatric disability or social, family, or geographic reason for which the patient may not be followed regularly PRIOR CONCURRENT THERAPY: * At least 7 days since prior CYP3A4 inhibitors or inducers * At least 3 months since prior radiofrequency ablation * No prior chemotherapy * No prior sunitinib, sorafenib, or any other inhibitors of angiogenesis * No concurrent participation in another trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Occurrence of Severe Bleeding and/or Liver Failure | Up to 7 days following each TACE, up to 5 months of treatment | The number of patients with at least one bleed and/or liver failure by treatment group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From randomization until death or last news for alive patients, up to 3 years | Overall survival is defined as the time from the date of randomization to the date of death (from any cause). Patients lost to follow-up or alive at the time of analysis are censored at the last news date or the point date. This time is used to calculate the median follow-up time. |
| Disease-free Survival | From randomization until the date of first progression (clinical or radiological) or death from any cause whichever came first | Disease-free survival is defined as the time interval between randomization and local or distant relapse or second cancer or death (all causes). Alive patients are censored at the last follow-up. |
Countries
France
Participant flow
Recruitment details
78 patients were included by 17 centers
Participants by arm
| Arm | Count |
|---|---|
| Placebo placebo 3cps/days 4 weeks over 6 during 1 year
Placebo: placebo 3cps/days 4 weeks over 6 during 1 year
transarterial chemoembolization: Chemoembolisation | 39 |
| Sunitinib sunitinib (SUTENT®) 37.5 mg/d (3 cps of 12.5 mg) orally 4 weeks over 6 (4 weeks of treatment followed by 2 weeks without treatment) during 1 year
sunitinib malate: placebo 3cps/days 4 weeks over 6 during 1 year
transarterial chemoembolization: Chemoembolisation | 39 |
| Total | 78 |
Baseline characteristics
| Characteristic | Sunitinib | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 65.97 years | 66.44 years | 67.4 years |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment France | 39 participants | 78 participants | 39 participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 4 Participants |
| Sex: Female, Male Male | 36 Participants | 71 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 32 / 39 | 30 / 38 |
| other Total, other adverse events | 27 / 39 | 36 / 38 |
| serious Total, serious adverse events | 14 / 39 | 13 / 38 |
Outcome results
Primary
Percentage of Patients With Occurrence of Severe Bleeding and/or Liver Failure
The number of patients with at least one bleed and/or liver failure by treatment group
Time frame: Up to 7 days following each TACE, up to 5 months of treatment
Population: Intent to treat modified population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Patients With Occurrence of Severe Bleeding and/or Liver Failure | 5.88 percentage of participants |
| Sunitinib | Percentage of Patients With Occurrence of Severe Bleeding and/or Liver Failure | 2.78 percentage of participants |
Secondary
Disease-free Survival
Disease-free survival is defined as the time interval between randomization and local or distant relapse or second cancer or death (all causes). Alive patients are censored at the last follow-up.
Time frame: From randomization until the date of first progression (clinical or radiological) or death from any cause whichever came first
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Disease-free Survival | 5.5 Months |
| Sunitinib | Disease-free Survival | 9 Months |
Secondary
Overall Survival
Overall survival is defined as the time from the date of randomization to the date of death (from any cause). Patients lost to follow-up or alive at the time of analysis are censored at the last news date or the point date. This time is used to calculate the median follow-up time.
Time frame: From randomization until death or last news for alive patients, up to 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Overall Survival | 20.5 Months |
| Sunitinib | Overall Survival | 25 Months |