Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
drksid header

  DRKS00003671

Trial Description

start of 1:1-Block title

Title

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)

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

REACH

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

[---]*

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

This is a Phase 3 multicenter, randomized study evaluating the safety and efficacy of
ramucirumab DP plus BSC as a double-blind, placebo-controlled (placebo plus BSC) comparison.

Approximately 544 patients, at least 18 years of age, with Child-Pugh score < 7 and
diagnosed with hepatocellular carcinoma will be randomized. Patients must have received
sorafenib as first-line systemic treatment for HCC, and must have discontinued sorafenib
prior to entering the study.

Hypothesis: This sample size will allow differentiation of the expected increase in median
OS, from 8 months in the placebo arm to 10.67 months in the ramucirumab arm.

Upon registration and completion of screening procedures, eligible patients with HCC who
have disease progression during or following first-line therapy with sorafenib, or were
intolerant to this agent, will be randomized to receive either ramucirumab DP or placebo.

The treatment regimen will be continued until radiographic or symptomatic progression, the
development of unacceptable toxicity, noncompliance or withdrawal of consent by the patient,
or investigator decision.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

[---]*

end of 1:1-Block scientific synopsis
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00003671
  •   2012/05/09
  •   2010/06/02
  •   no
  •   [---]*
  •   [---]*
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   2010-019318-26 
  •   NCT01140347  (ClinicalTrials.gov)
  •   13895  (ImClone LLC)
  •   CP12-0919 
  •   I4T-IE-JVBF 
  •   2010-019318-26 
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   Hepatocellular Carcinoma
  •   C22.0 -  Malignant neoplasm: Liver cell carcinoma
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Biological: Placebo
  •   Biological: Ramucirumab DP (IMC-1121B)
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, investigator/therapist
  •   Placebo
  •   Treatment
  •   Parallel
  •   III
  •   [---]*
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

- Overall survival (OS) - Time from the date of randomization to the date of death from any cause; time frame: Approximately 43 months

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

- Progression-free survival (PFS); time frame: Approximately 43 months
- Objective response rate (ORR); time frame: Approximately 43 months
- Time to radiographic progression; time frame: Approximately 43 months
- Change in the Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8); time frame: Approximately 43 months
- Change in EuroQol EQ-5D, change from baseline in the patient reported outcomes measured at the end of therapy visit; time frame: Approximately 43 months
- Number of Participants with Adverse Events (AEs); time frame: Approximately 43 months
- Maximum concentration (Cmax) cycle 1; time frame: Day 1
- Maximum concentration (Cmax) cycle 4; time frame: 6 weeks
- Maximum concentration (Cmax) cycle 7; time frame: 12 weeks
- Serum Anti-ramucirumab Antibody Assessment (Immunogenicity); time frame: Approximately 43 months

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   United States
  •   Australia
  •   Austria
  •   Belgium
  •   Brazil
  •   Bulgaria
  •   Canada
  •   Czech Republic
  •   Finland
  •   France
  •   Germany
  •   Hong Kong
  •   Hungary
  •   Israel
  •   Italy
  •   Japan
  •   Korea, Republic of
  •   Netherlands
  •   Norway
  •   Philippines
  •   Portugal
  •   Romania
  •   Spain
  •   Sweden
  •   Switzerland
  •   Taiwan, Province of China
  •   Thailand
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   [---]*
  •   2010/10/31
  •   544
  •   Multicenter trial
  •   International
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

Inclusion criteria:

- Eastern Cooperative Oncology Group Performance Status of 0 or 1

- Child-Pugh score of < 7 (Child-Pugh Class A only)

- Barcelona Clinic Liver Cancer (BCLC) stage C or BCLC stage B not amenable to
locoregional therapy or refractory to locoregional therapy

- Diagnosis of HCC (excluding fibrolamellar carcinoma) in the absence of histologic or
cytologic confirmation

- There are either clinical, laboratory, or radiographic findings consistent with a
diagnosis of liver cirrhosis

- Has a liver mass measuring at least 2 cm with characteristic vascularization seen on
either triphasic computed tomography (CT) scan or magnetic resonance imaging (MRI)
with gadolinium

- 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

- Previously treated with sorafenib and has discontinued sorafenib treatment at least
14 days prior to randomization. patients may have experienced:

- Radiographically documented disease progression during sorafenib therapy or
after discontinuation of sorafenib therapy, or

- Discontinuation of sorafenib due to an adverse drug reaction, despite dose
reduction by 1 level and BSC

- The patient has received sorafenib as the only systemic therapeutic intervention.
Any hepatic locoregional therapy that has been administered prior to sorafenib is
allowed, but not following sorafenib. Radiation to metastatic sites (eg, bone)
following sorafenib therapy is permitted.

- Resolution of clinically significant toxicity of any anti cancer therapy to grade ≤ 1
by the NCI-CTCAE v. 4.0

Adequate Organ Function defined as:

- Total bilirubin < 3.0 mg/dL (51.3 µmol/L), aspartate aminotransferase (AST) and
alanine aminotransferase (ALT) ≤ 5 × ULN

- Serum creatinine ≤ 1.2 × ULN or calculated creatinine clearance > 50 mL/minute

- Absolute neutrophil count (ANC) ≥ 1.0 × 10^3/μL (1.0 × 10^9/L), hemoglobin ≥ 9 g/dL
(5.58 mmol/L), and platelets ≥ 75 × 10^3/µL (75 × 10^9/L)

- International Normalized Ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) ≤ 5
seconds above ULN. Patients receiving prophylactic low-dose anticoagulant therapy are
eligible provided that INR ≤ 1.5 and PTT ≤ 5 seconds above the upper limit of normal
(ULN)

- The patient's urinary protein is ≤ 1+ on dipstick or routine urinalysis. If urine
dipstick or routine analysis indicates ≥ 2+ proteinuria, then a 24-hour urine must be
collected and must demonstrate < 1000 mg of protein in 24 hours to allow
participation in the study

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

Exclusion Criteria

Exclusion criteria:

- Major surgery within 28 days prior to randomization, or central venous access device
placement within 7 days prior to randomization

- Hepatic locoregional therapy within 28 days prior to randomization

- Radiation to any nonhepatic (eg, bone) site within 14 days prior to randomization

- Sorafenib within 14 days prior to randomization

- Received any investigational therapy or non-approved drug within 28 days prior to
randomization

- Received any previous systemic therapy with vascular endothelial growth factor (VEGF)
inhibitors or vascular endothelial growth factor receptor (VEGFR) inhibitors
(including investigational agents) other than sorafenib for treatment of HCC

- Fibrolamellar carcinoma

- Received any transfusion, blood component preparation, erythropoietin, albumin
preparation, or granulocyte colony-stimulating factors (G-CSF) within 14 days prior
to randomization

- 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 and PTT ≤ 5 seconds above the upper limit of normal [ULN]) are met

- Receiving ongoing therapy with nonsteroidal anti-inflammatory agents (NSAIDs, eg,
indomethacin, ibuprofen, naproxen, nimesulide, celecoxib, etoricoxib, or similar
agents) or other antiplatelet agents (eg, clopidogrel, ticlopidine, prasugrel,
dipyridamole, picotamide, indobufen, anagrelide, triflusal).Aspirin (ASA) at doses up
to 100 mg/day is permitted

- Symptomatic congestive heart failure, unstable angina pectoris, or symptomatic or
poorly controlled cardiac arrhythmia

- Any arterial thrombotic event, including myocardial infarction, unstable angina,
cerebrovascular accident, or transient ischemic attack, within 6 months prior to
randomization

- Uncontrolled arterial hypertension ≥ 150 / ≥ 90 mm Hg despite standard medical
management

- 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)

- Esophageal or gastric varices that require immediate intervention (eg, banding,
sclerotherapy) or represent a high bleeding risk. Patients with evidence of portal
hypertension (including splenomegaly) or any prior history of variceal bleeding must
have had endoscopic evaluation within the 3 months immediately prior to
randomization. Patients 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, these eligible patients must receive supportive therapy (eg, beta blocker
therapy) according to institutional standards and clinical guidelines during study
participation

- Central nervous system (CNS) metastases or carcinomatous meningitis

- History of or current hepatic encephalopathy or current clinically meaningful ascites

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Eli Lilly and Company
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • Eli Lilly and Company
    • Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) 
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Eli Lilly and Company
    • Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) 
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting complete, follow-up continuing
  •   [---]*
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  • [---]*
end of 1:n-Block publications
The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   8
  •   2013/10/30
* This entry means the parameter is not applicable or has not been set.