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NCT01140347 · CITED IN SOURCE DOCUMENTS

A Study of Ramucirumab (IMC-1121B) Drug Product (DP) and Best Supportive Care (BSC) Versus Placebo and BSC as 2nd-Line Treatment in Participants With Hepatocellular Carcinoma After 1st-Line Therapy With Sorafenib

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2015-12-28

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 participants, at least 18 years of age, with Child-Pugh score \< 7 and diagnosed with hepatocellular carcinoma will be randomized. Participants must have received sorafenib as first-line systemic treatment for hepatocellular carcinoma (HCC), and must have discontinued sorafenib prior to entering the study. Hypothesis: This sample size will allow differentiation of the expected increase in median overall survival (OS), from 8 months in the placebo arm to 10.67 months in the ramucirumab arm. Upon registration and completion of screening procedures, eligible participants 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 participant, or investigator decision.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Progression-Free Survival (PFS)

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outcome · POSTED

Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]

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outcome · POSTED

Time to Radiographic Progression (TTP)

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outcome · POSTED

Change From Baseline in the Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8)

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outcome · POSTED

Change From Baseline in European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score

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outcome · POSTED

Number of Participants With Adverse Events (AEs) and the Number of Participants Who Died

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outcome · POSTED

Maximum Concentration (Cmax) of Ramucirumab, Cycle 1

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outcome · POSTED

Cmax of Ramucirumab, Cycle 4

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outcome · POSTED

Cmax of Ramucirumab, Cycle 7

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outcome · POSTED

Number of Participants With Treatment Emergent Positive Anti-Ramucirumab Response [Serum Anti-Ramucirumab Antibody Assessment (Immunogenicity)]

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Inclusion criteria: * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 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 centimeters (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 \[that is (i.e.), is vascularized\], 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. Participants 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 participant 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 \[for example (e.g.), bone\] following sorafenib therapy is permitted. * Resolution of clinically significant toxicity of any anti-cancer therapy to Grade ≤1 by the National Cancer Institute Common Terminology Criteria for Adverse Events volume 4.0 (NCI-CTCAE v. 4.0). Adequate Organ Function defined as: * Total bilirubin \<3.0 milligrams/deciliter (mg/dL) \[51.3 micromole/liter (µmol/L)\], aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 × upper limit of normal (ULN) * Serum creatinine ≤1.2 × ULN or calculated creatinine clearance \>50 milliliters/minute (mL/min) * Absolute neutrophil count (ANC) ≥1.0 × 10\^3/microliter (μL) (1.0 × 10\^9/liter (L)\]), hemoglobin ≥9 grams/deciliter (g/dL) \[5.58 millimoles/liter (mmol/L)\], 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. Participants receiving prophylactic low-dose anticoagulant therapy are eligible provided that INR ≤1.5 and PTT ≤5 seconds above the ULN * The participant'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 milligrams (mg) of protein in 24 hours to allow participation in the study 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 (e.g., 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. Participants 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 ULN) are met * Receiving ongoing therapy with nonsteroidal anti-inflammatory agents (NSAIDs, e.g., indomethacin, ibuprofen, naproxen, nimesulide, celecoxib, etoricoxib, or similar agents) or other antiplatelet agents (e.g., clopidogrel, ticlopidine, prasugrel, dipyridamole, picotamide, indobufen, anagrelide, triflusal). Aspirin (ASA) at doses up to 100 milligrams/day (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 systolic ≥150 / diastolic ≥90 millimeters of mercury (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 (participants 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 (e.g., banding, sclerotherapy) or represent a high bleeding risk. Participants 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. Participants 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 participants must receive supportive therapy (e.g., 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
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. intervention Names
    1. Biological: Ramucirumab DP (IMC-1121B)
    2. Other: BSC
    label
    Ramucirumab DP and BSC
    type
    EXPERIMENTAL
  2. intervention Names
    1. Biological: Placebo
    2. Other: BSC
    label
    Placebo and BSC
    type
    PLACEBO_COMPARATOR
interventions
  1. arm Group Labels
    1. Placebo and BSC
    description
    8 mg/kg IV every 2 weeks
    name
    Placebo
    type
    BIOLOGICAL
  2. arm Group Labels
    1. Ramucirumab DP and BSC
    description
    8 milligrams/kilogram (mg/kg) intravenous (IV) every 2 weeks
    name
    Ramucirumab DP (IMC-1121B)
    other Names
    1. IMC-1121B
    2. LY3009806
    type
    BIOLOGICAL
  3. arm Group Labels
    1. Placebo and BSC
    2. Ramucirumab DP and BSC
    description
    Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
    name
    BSC
    type
    OTHER
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
DOUBLE
who Masked
  1. PARTICIPANT
  2. INVESTIGATOR
primary Purpose
TREATMENT
Enrollment
count
565
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    OS was defined as the time from the date of randomization to the date of death from any cause. Participants who were alive at the end of the follow-up period or were lost to follow-up were censored on the last date the participant was known to be alive.
    measure
    Overall Survival (OS)
    time Frame
    Randomization to death from any cause (up to 37 months)
secondary Outcomes
  1. description
    PFS was defined as time from date of randomization until date of objectively determined progressive disease (PD) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 or death from any cause. PD was defined as ≥20% increase in sum of diameters (SOD) of target lesions, taking as reference smallest sum on study (including baseline sum if it was smallest). Sum must show a ≥5 millimeter (mm) increase. Appearance of ≥1 new lesions and unequivocal progression of existing non-target lesions were considered progression. In primary analysis, participants alive and without PD were censored at day of last adequate tumor assessment; progression or deaths without progression occurring immediately after ≥2 missed tumor assessments, were censored at day of the last adequate tumor assessment prior to missing assessments; participants who began new anticancer therapy were censored at day of the last adequate tumor assessment prior to start of new anticancer therapy.
    measure
    Progression-Free Survival (PFS)
    time Frame
    Randomization to PD (up to 36 months)
  2. description
    ORR was defined, using RECIST v1.1 criteria, as the percentage of participants who achieved a best overall response of CR or PR. CR was defined as the disappearance of all lesions and any intratumor arterial enhancement in target lesions, the normalization of the tumor marker level and all lymph nodes short axis reduced to \<10 mm. PR was defined as ≥30% decrease in the SOD of target lesions, including the short axes of any target lymph nodes, taking as reference the baseline SOD of target lesions, no new lesions and stable nontarget lesions. Percentage of participants was calculated as: (number of participants with CR or PR / number of participants randomized) \* 100.
    measure
    Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
    time Frame
    Baseline to the date of first evidence of confirmed CR or PR (up to 37 months)
  3. description
    TTP was defined as the time from randomization to the first radiographically documented PD. PD was defined, using RECIST v1.1 criteria, as ≥20% increase in SOD of target lesions, taking as reference smallest sum on study (including baseline sum if it was the smallest). Sum must show an absolute increase of ≥5 mm. Appearance of ≥1 new lesions and unequivocal progression of existing non-target lesions were considered progression. Participants without PD were censored at the day of the last adequate tumor assessment. Progression occurred immediately after ≥2 missed tumor assessments and were censored at the day of the last adequate tumor assessment prior to the missing assessments. Participants who began new anticancer therapy were censored at the day of their last adequate tumor assessment prior to start of new anticancer therapy.
    measure
    Time to Radiographic Progression (TTP)
    time Frame
    Randomization to PD (up to 36 months)
  4. description
    The FHSI-8 is a self-administered 8-item questionnaire that measures a participant's symptoms in the domains of jaundice, stomach pain/discomfort weight loss, and fatigue. Participants rated each item on a 5-point scale from 0 (not at all) to 4 (very much). Item scores were calculated as outlined in the FACIT manual. FHSI-8 total score was the sum of each item's score with a total score ranging from 0 (highly symptomatic) to 32 (asymptomatic).
    measure
    Change From Baseline in the Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8)
    time Frame
    Baseline, Prior to infusion on Day 1 of Cycle 4, Cycle 10, and Cycle 16 (14-day cycles), and end of treatment (up to 34 months)
  5. description
    The EQ-5D is a self-reported, 5-dimension (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) questionnaire related to the participant's current health state. Each question was scored using a 3 level scale (no problems, some problems, or extreme problems). EQ-5D health state was defined by combining responses from each of the 5 dimensions into a weighted health-state index score according to the United Kingdom (UK) population based algorithm where 0 = death and 1 = perfect health.
    measure
    Change From Baseline in European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score
    time Frame
    Baseline, Prior to infusion on Day 1 of Cycle 4, Cycle 10, and Cycle 16 (14-day cycles), end of treatment (up to 34 months)
  6. description
    The number of participants with serious AEs (SAEs), other non-serious AEs and participants who died. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
    measure
    Number of Participants With Adverse Events (AEs) and the Number of Participants Who Died
    time Frame
    Baseline to study completion (up to 37 months)
  7. measure
    Maximum Concentration (Cmax) of Ramucirumab, Cycle 1
    time Frame
    1 hour following the completion of Cycle 1 (14-day cycle) infusion
  8. measure
    Cmax of Ramucirumab, Cycle 4
    time Frame
    1 hour following completion of Cycle 4 (14-day cycles) infusion
  9. measure
    Cmax of Ramucirumab, Cycle 7
    time Frame
    1 hour following completion of Cycle 7 (14-day cycles) infusion
  10. description
    Participants were considered positive for anti-ramucirumab antibodies \[anti-drug antibodies (ADA)\] if the post-treatment sample had an increase of at least 4-fold in titer from the pretreatment values. If the pretreatment value was not detected or was not present, a 1:20 post-treatment titer was required to indicate treatment emergence of ADA.
    measure
    Number of Participants With Treatment Emergent Positive Anti-Ramucirumab Response [Serum Anti-Ramucirumab Antibody Assessment (Immunogenicity)]
    time Frame
    Prior to treatment and 1 hour post end of infusion for Cycles 1, 4 and 7 (14-day cycles)
Full study description
brief Summary
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 participants, at least 18 years of age, with Child-Pugh score \< 7 and diagnosed with hepatocellular carcinoma will be randomized. Participants must have received sorafenib as first-line systemic treatment for hepatocellular carcinoma (HCC), and must have discontinued sorafenib prior to entering the study. Hypothesis: This sample size will allow differentiation of the expected increase in median overall survival (OS), from 8 months in the placebo arm to 10.67 months in the ramucirumab arm. Upon registration and completion of screening procedures, eligible participants 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 participant, or investigator decision.
Source references
references
  1. citation
    Llovet JM, Singal AG, Villanueva A, Finn RS, Kudo M, Galle PR, Ikeda M, Callies S, McGrath LM, Wang C, Abada P, Widau RC, Gonzalez-Gugel E, Zhu AX. Prognostic and Predictive Factors in Patients with Advanced HCC and Elevated Alpha-Fetoprotein Treated with Ramucirumab in Two Randomized Phase III Trials. Clin Cancer Res. 2022 Jun 1;28(11):2297-2305. doi: 10.1158/1078-0432.CCR-21-4000.
    pmid
    35247922
    type
    DERIVED
  2. citation
    Mitani S, Chen Y, Inoue K, Mori J, Gao L, Long A, Wakabayashi S. Clinical Impact of a Shortened Infusion Duration of Ramucirumab in Japanese Patients -A Model-Based Approach. Gan To Kagaku Ryoho. 2021 Nov;48(11):1381-1387.
    pmid
    34795131
    type
    DERIVED
  3. citation
    Zhu AX, Finn RS, Kang YK, Yen CJ, Galle PR, Llovet JM, Assenat E, Brandi G, Motomura K, Ohno I, Daniele B, Vogel A, Yamashita T, Hsu CH, Gerken G, Bilbruck J, Hsu Y, Liang K, Widau RC, Wang C, Abada P, Kudo M. Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab. Br J Cancer. 2021 Apr;124(8):1388-1397. doi: 10.1038/s41416-021-01260-w. Epub 2021 Feb 3.
    pmid
    33531690
    type
    DERIVED
  4. citation
    Reig M, Galle PR, Kudo M, Finn R, Llovet JM, Metti AL, Schelman WR, Liang K, Wang C, Widau RC, Abada P, Zhu AX. Pattern of progression in advanced hepatocellular carcinoma treated with ramucirumab. Liver Int. 2021 Mar;41(3):598-607. doi: 10.1111/liv.14731. Epub 2020 Dec 5.
    pmid
    33188713
    type
    DERIVED
  5. citation
    Zhu AX, Nipp RD, Finn RS, Galle PR, Llovet JM, Blanc JF, Okusaka T, Chau I, Cella D, Girvan A, Gable J, Bowman L, Wang C, Hsu Y, Abada PB, Kudo M. Ramucirumab in the second-line for patients with hepatocellular carcinoma and elevated alpha-fetoprotein: patient-reported outcomes across two randomised clinical trials. ESMO Open. 2020 Aug;5(4):e000797. doi: 10.1136/esmoopen-2020-000797.
    pmid
    32817068
    type
    DERIVED
  6. citation
    Kudo M, Okusaka T, Motomura K, Ohno I, Morimoto M, Seo S, Wada Y, Sato S, Yamashita T, Furukawa M, Aramaki T, Nadano S, Ohkawa K, Fujii H, Kudo T, Furuse J, Takai H, Homma G, Yoshikawa R, Zhu AX. Ramucirumab after prior sorafenib in patients with advanced hepatocellular carcinoma and elevated alpha-fetoprotein: Japanese subgroup analysis of the REACH-2 trial. J Gastroenterol. 2020 Jun;55(6):627-639. doi: 10.1007/s00535-020-01668-w. Epub 2020 Feb 27.
    pmid
    32107609
    type
    DERIVED
  7. citation
    Arnold D, Fuchs CS, Tabernero J, Ohtsu A, Zhu AX, Garon EB, Mackey JR, Paz-Ares L, Baron AD, Okusaka T, Yoshino T, Yoon HH, Das M, Ferry D, Zhang Y, Lin Y, Binder P, Sashegyi A, Chau I. Meta-analysis of individual patient safety data from six randomized, placebo-controlled trials with the antiangiogenic VEGFR2-binding monoclonal antibody ramucirumab. Ann Oncol. 2017 Dec 1;28(12):2932-2942. doi: 10.1093/annonc/mdx514.
    pmid
    28950290
    type
    DERIVED
  8. citation
    Chau I, Peck-Radosavljevic M, Borg C, Malfertheiner P, Seitz JF, Park JO, Ryoo BY, Yen CJ, Kudo M, Poon R, Pastorelli D, Blanc JF, Chung HC, Baron AD, Okusaka T, Bowman L, Cui ZL, Girvan AC, Abada PB, Yang L, Zhu AX. Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib: Patient-focused outcome results from the randomised phase III REACH study. Eur J Cancer. 2017 Aug;81:17-25. doi: 10.1016/j.ejca.2017.05.001. Epub 2017 Jun 4.
    pmid
    28591675
    type
    DERIVED
  9. citation
    Zhu AX, Baron AD, Malfertheiner P, Kudo M, Kawazoe S, Pezet D, Weissinger F, Brandi G, Barone CA, Okusaka T, Wada Y, Park JO, Ryoo BY, Cho JY, Chung HC, Li CP, Yen CJ, Lee KD, Chang SC, Yang L, Abada PB, Chau I. Ramucirumab as Second-Line Treatment in Patients With Advanced Hepatocellular Carcinoma: Analysis of REACH Trial Results by Child-Pugh Score. JAMA Oncol. 2017 Feb 1;3(2):235-243. doi: 10.1001/jamaoncol.2016.4115.
    pmid
    27657674
    type
    DERIVED
  10. citation
    Kudo M, Hatano E, Ohkawa S, Fujii H, Masumoto A, Furuse J, Wada Y, Ishii H, Obi S, Kaneko S, Kawazoe S, Yokosuka O, Ikeda M, Ukai K, Morita S, Tsuji A, Kudo T, Shimada M, Osaki Y, Tateishi R, Sugiyama G, Abada PB, Yang L, Okusaka T, Zhu AX. Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma: Japanese subgroup analysis of the REACH trial. J Gastroenterol. 2017 Apr;52(4):494-503. doi: 10.1007/s00535-016-1247-4. Epub 2016 Aug 22.
    pmid
    27549242
    type
    DERIVED
  11. citation
    Zhu AX, Park JO, Ryoo BY, Yen CJ, Poon R, Pastorelli D, Blanc JF, Chung HC, Baron AD, Pfiffer TE, Okusaka T, Kubackova K, Trojan J, Sastre J, Chau I, Chang SC, Abada PB, Yang L, Schwartz JD, Kudo M; REACH Trial Investigators. Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2015 Jul;16(7):859-70. doi: 10.1016/S1470-2045(15)00050-9. Epub 2015 Jun 18.
    pmid
    26095784
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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        abindex="-1">Evidence (ramucirumab):</p> <div class="pdq-content-list"><ol id="_483"><li>The <a href="/clinicaltrials/NCT01140347">REACH</a> trial (NCT01140347) randomly assigned 565 patients with advanced HCC to receive either ramucirumab or placebo after first-line sorafenib. The primary end point was OS.[<a href="#
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      1. context
        Updated: April 17, 2025
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    Preserved source evidence · Not medical advice