A Multicenter, Randomized, Double-Blind, Phase 3 Study of Ramucirumab (IMC-1121B) Drug Product and Best Supportive Care (BSC) Versus Placebo and BSC as Second-Line Treatment in Patients With Hepatocellular Carcinoma Following First-Line Therapy With Sorafenib - REACH
- Conditions
- Hepatocellular CarcinomaMedDRA version: 12.1Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectable
- Registration Number
- EUCTR2010-019318-26-FR
- Lead Sponsor
- ImClone LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 565
1. The patient has provided signed informed consent and is amenable to compliance with protocol schedules and testing.
2. The patient is at least 18 years of age.
3. The patient has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
4. The patient has a Child-Pugh score of < 9 (Child-Pugh A or B [B7 or B8]).
5. The patient has a Barcelona Clinic Liver Cancer (BCLC) stage C at randomization. A patient with BCLC stage B may be eligible if he/she has disease that is not amenable to locoregional therapy or is refractory to locoregional therapy (examples include very large or diffusely infiltrative tumors and intrahepatic tumors that are refractory to transarterial chemoembolization [TACE] or not amenable to TACE).
6. The patient has a diagnosis of HCC (excluding fibrolamellar carcinoma) based on
histopathologic or cytologic findings; or in the absence of histologic confirmation, all of the following are present (at the time of study entry):
a. There are either clinical, laboratory, or radiographic findings consistent with a diagnosis of liver cirrhosis,
b. The patient has a liver mass measuring at least 2 cm with characteristic vascularization (intense inhomogeneous enhancement seen in the hepatic arterial-dominant phase and contrast washout in the late portal venous phase) seen on either triphasic computed tomography (CT) scan or magnetic resonance imaging (MRI) with gadolinium,
c. The patient has a serum alpha-fetoprotein (AFP) concentration greater than the institutional upper limit of normal (ULN).
7. The patient has at least 1 measurable or evaluable lesion that is viable (ie, is vascularized), and has not been previously treated with locoregional therapy. A lesion that has been previously treated will qualify as a measurable or evaluable lesion if there was demonstrable progression following locoregional therapy.
8. The patient has previously been treated with sorafenib and has discontinued sorafenib treatment at least 14 days prior to randomization. This will include patients who have experienced:
a. Radiographically documented disease progression during sorafenib therapy or after discontinuation of sorafenib therapy, or
b. Discontinuation of sorafenib due to an adverse drug reaction (fatigue, hand-foot syndrome, desquamation/rash, diarrhea, reversible liver dysfunction, abdominal pain, anorexia, or leukopenia), despite dose reduction by 1 level and BSC.
9. The patient has received sorafenib as the most recent systemic therapeutic intervention. Any hepatic locoregional therapy (including radiation, surgery, hepatic arterial embolization, chemoembolization, radiofrequency ablation, cryoablation, percutaneous ethanol injection) that has been administered prior to sorafenib is allowed, but not following sorafenib. Radiation to metastatic sites (eg, bone) following sorafenib therapy is permitted.
10. The patient has resolution to Grade = 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.02 (NCI-CTCAE v 4.02) of all clinically significant toxic effects of prior locoregional therapy, surgery, chemoembolization, or other anticancer therapy, including sorafenib.
11. The patient has adequate organ function defined as:
a. Total bilirubin < 3.0 mg/dL (51.3 µmol/L), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 5 × ULN;
b. Serum creatinine = 1.2 × ULN or calculated creatinine clearance > 50 mL/minute;
c. Absolute neutrophil count (ANC) = 1.0 × 10 exp3
1. The patient (P) has undergone major surgery within 28 days prior to randomization, or subcutaneous venous access device placement within 7 days prior to randomization.
2. Hepatic locoregional therapy (including radiation, surgery, hepatic arterial embolization, chemoembolization, radiofrequency ablation, cryoablation, or percutaneous ethanol injection) within 28 days prior to randomization
3. Radiation to any nonhepatic site within 14 days prior to randomization
4. Sorafenib within 14 days prior to randomization
5. Any investigational therapy within 28 days prior to randomization
6. Any previous systemic therapy with vascular endothelial growth factor inhibitors or vascular endothelial growth factor receptor inhibitors (including investigational agents) other than sorafenib for treatment of HCC
7. Fibrolamellar carcinoma
8. Any transfusion, blood component preparation, erythropoietin, albumin preparation, or granulocyte colony-stimulating factors within 14 days prior to randomization
9. P is receiving therapeutic anticoagulation with warfarin, low-molecular-weight heparin, or similar agents. Patients receiving prophylactic, low-dose anticoagulation therapy are eligible provided that the coagulation parameters defined in the inclusion criteria (INR = 1.5) are met.
10. P is receiving ongoing therapy with nonsteroidal anti-inflammatory agents (NSAIDs, eg, indomethacin, ibuprofen, naproxen, or similar agents) or other antiplatelet agents (eg, clopidogrel, ticlopidine, dipyridamole, anagrelide). Aspirin at doses of 325 mg/day or below is permitted.
11. Symptomatic congestive heart failure, unstable angina pectoris, or symptomatic or poorly controlled cardiac arrhythmia.
12. Any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization.
13. Uncontrolled arterial hypertension = 150 / = 90 mm Hg despite standard medical management
14. Any Grade 3-4 gastrointestinal bleeding or any variceal bleeding episode in the 3 months prior to randomization requiring transfusion, endoscopic or operative intervention (patients with any bleeding episode considered life-threatening during the 3 months prior to randomization are excluded, regardless of transfusion or intervention status)
15. Esophageal or gastric varices that require immediate intervention (eg, banding, sclerotherapy) or represent a high bleeding risk in the opinion of the investigator or consulting gastroenterologist or hepatologist. P.s with evidence of portal hypertension (defined as splenomegaly, platelets < 100 × 10 exp3/µL [100 × 10 exp9/L], or any prior history of variceal bleeding) must have had endoscopic evaluation within the 3 months immediately prior to randomization.
P.s with evidence of portal hypertension are eligible for study participation if endoscopic evaluation does not indicate esophageal or gastric varices that require immediate intervention or represent a high bleeding risk; however, they must receive supportive therapy (eg, beta blocker therapy) according to institutional standards and clinical guidelines during study participation. Additional endoscopic assessments during study participation should be performed at the discretion of the consulting gastroenterologist or hepatologist, as clinically indicated.
16. CNS metastases or carcinomatous meningitis
17. Serious illness or medical condition(s), including but not limited to the following:
a. Known HIV i
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method