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CompletedNCT02435433REACH-2Updated Jan 20, 2023Results posted

A Study of Ramucirumab (LY3009806) Versus Placebo in Participants With Hepatocellular Carcinoma and Elevated Baseline Alpha-Fetoprotein

A Phase 3 interventional study of Ramucirumab and Placebo in Hepatocellular Carcinoma, sponsored by Eli Lilly and Company. Completed at 131 sites in 20 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-01-20.

Sponsored by Eli Lilly and Company · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
399
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to evaluate the safety and efficacy of ramucirumab in participants with hepatocellular carcinoma (HCC) and elevated baseline alpha-fetoprotein. Participants will be randomized to ramucirumab or placebo in a 2:1 ratio (Main Global Cohort and China Maximized Extended Enrollment [MEE] Cohort). Participants may also receive ramucirumab if eligible to be enrolled in Open-Label Expansion (OLE) Cohort.

02

Conditions studied

  • Hepatocellular Carcinoma

Keywords

  • liver cancer
03

In context

Carcinoma, Hepatocellular

3,249 studies on the registry are indexed under Carcinoma, Hepatocellular; 974 are open to participants now.

This study's enrollment of 399 is above the median of 55 across 2,347 interventional studies indexed under Carcinoma, Hepatocellular.

Browse Carcinoma, Hepatocellular studies →

Lead sponsor

Eli Lilly and Company is the lead sponsor of 2,095 studies on the registry; 142 are open to participants now.

Of its 535 completed or terminated interventional studies of FDA-regulated products, 356 (67%) have results posted.

Browse Eli Lilly and Company studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • A diagnosis of HCC based on histopathologic findings, or a diagnosis of cirrhosis and a tumor with classical HCC imaging characteristics.
  • Sorafenib was the only systemic therapy for HCC and was discontinued for disease progression or intolerance (Main Global and MEE Cohorts only).
  • The participant received ≤2 prior systemic therapy regimen, excluding prior sorafenib or chemotherapy, for the treatment of HCC (OLE Cohort only).
  • ≥1 measurable lesion per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 that has not been previously treated with locoregional therapy. A participant with a lesion(s) that has previously been treated with locoregional therapy is also eligible, if the lesion has documented progression after locoregional treatment and is measureable.
  • Child-Pugh score \<7 (Child-Pugh Class A).
  • Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy.
  • Baseline AFP ≥400 nanograms/milliliter.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Resolution of all clinically significant toxic effects of prior therapy.
  • Total bilirubin ≤1.5 times upper limit of normal value (ULN), aspartate transaminase (AST) and alanine transaminase (ALT) ≤5 × ULN.
  • Creatinine clearance ≥60 milliliters/minute.
  • Urinary protein is ≤1+ on dipstick or routine urinalysis or 24-hour urine demonstrating \<1 gram of protein.
  • Absolute neutrophil count ≥1.0 × 10\^9/Liter, hemoglobin ≥9 grams/deciliter, and platelets ≥75 × 10\^9/Liter.
  • International Normalized Ratio (INR) ≤1.5 and a partial thromboplastin time (PTT) ≤5 seconds above the ULN.
  • Surgically sterile, postmenopausal, or compliant with a highly effective contraceptive method.
  • If a woman of childbearing potential, a negative serum pregnancy test prior to randomization.
  • Willing to provide blood for research. The participant has provided signed informed consent prior to any study specific procedures and is amenable to compliance with protocol schedules and testing.

Exclusion criteria

Exclusion Criteria:

  • Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma.
  • Concurrent malignancy. Participants with carcinoma in situ of any origin and participants with prior malignancies in remission may be eligible with sponsor approval.
  • Previous brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression.
  • History of or current hepatic encephalopathy or clinically meaningful ascites.
  • Ongoing or recent hepatorenal syndrome.
  • Liver transplant (Main Global and MEE cohorts only; Participants with prior liver transplant may be eligible for OLE cohort).
  • Hepatic locoregional therapy following prior systemic therapy or within 28 days prior to randomization.
  • Major surgical procedure, traumatic injury, non-healing wound, or peptic ulcer ≤28 days prior to randomization.
  • Received radiation to any nonhepatic (for example, bone) site within 14 days prior to randomization.
  • Placement of a subcutaneous venous access device within 7 days prior to the first dose of study treatment unless the procedure is judged of low risk of bleeding.
  • Enrolled in a clinical trial involving an investigational product or unapproved use of a drug or in medical research judged not to be scientifically or medically compatible with this study.
  • Discontinued from study treatment from another clinical trial within 28 days prior to randomization.
  • Known allergy to any of the treatment components.
  • Uncontrolled hypertension.
  • Any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, \<6 months prior to randomization.
  • Any bleeding episode considered life-threatening, or any Grade 3 or 4 gastrointestinal bleeding episode in the 3 months prior to randomization requiring intervention.
  • Esophageal or gastric varices that require intervention or represent high bleeding risk. Participants with evidence of portal hypertension or prior bleeding must have had endoscopic evaluation within 3 months prior to randomization.
  • Gastrointestinal perforation or fistulae within 6 months prior to randomization.
  • Symptomatic congestive heart failure (New York Heart Association II-IV), unstable angina pectoris, or symptomatic or poorly controlled cardiac arrhythmia.
  • Pregnant or breast-feeding.

  • Any medical or psychiatric condition that may increase the risk associated with study participation or may interfere with the interpretation of study results. Conditions include but are not limited to:

    • Human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness.
    • Active or uncontrolled clinically serious infection. (Participants with chronic viral hepatitis are eligible.)
    • Ongoing or recent history of drug abuse.
    • Uncontrolled hereditary or acquired thrombotic or bleeding disorder.
  • Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection.
  • Therapeutic dose anticoagulation with warfarin, low molecular-weight heparin, or similar agents.
  • Chronic therapy with nonsteroidal anti-inflammatory agents or other anti-platelet agents. Aspirin at doses up to 100 milligrams/day is permitted.

  • The participant received prior immunotherapy and is experiencing or has experienced any of the following (OLE cohort only):

    • Any clinically significant Grade ≥3 immune-related adverse event (irAE)
    • Any grade neurologic or ocular irAE
    • Any grade immune-related pneumonitis, cardiomyopathy, or hepatitis
  • The participant received prior immunotherapy and at the time of study enrollment, requires steroids or other immunosuppressive agents (OLE cohort only).
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
399 participants (actual)

Study arms

  • Experimental
    Ramucirumab + Best Supportive Care (BSC)

    8 milligrams per kilogram (mg/kg) ramucirumab administered as an intravenous (IV) injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

    Drug: Ramucirumab

  • Placebo comparator
    Placebo + BSC

    Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

    Drug: Ramucirumab · Drug: Placebo

  • Experimental
    Open Label Ramucirumab + BSC

    8 mg/kg ramucirumab administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

    Drug: Ramucirumab

  • Experimental
    Ramucirumab MEE Cohort + BSC

    8 mg/kg ramucirumab administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

    Drug: Ramucirumab

  • Placebo comparator
    Placebo MEE Cohort + BSC

    Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

    Drug: Ramucirumab · Drug: Placebo

Interventions

  • DrugRamucirumab

    Administered IV

    Also known as: Cyramza, LY3009806

  • DrugPlacebo

    Administered IV

06

What researchers measure

Primary outcomes

  1. Overall Survival (OS)

    OS time was measured from date of randomization to date of death from any cause. Participants who were not known to have died on or before the date of data cut-off, OS data was censored on the last date (on or before the cut-off date) the participant was known to be alive.

    Time frame: From Date of Randomization to Death from Any Cause (Up to 28 Months)

Secondary outcomes

  1. Progression Free Survival (PFS)

    Progression-free survival is defined as time from the date of randomization to the date of first observation of objective progression or death from any cause.

    Time frame: From Randomization to Objective Progression or Death from Any Cause (Up to 28 Months)

  2. Time to Radiographic Progression

    Time to radiographic progression is defined as the time from the date of randomization to the date of first observation of objective progression.

    Time frame: From Randomization to Objective Progression (Up to 28 Months)

  3. Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)

    Objective response rate is defined as the percentage of participants who achieve a best overall response of complete response (CR) + partial response (PR). ORR = CR + PR. CR is the disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Tumor marker results must have normalized. Best overall response is classified based on the overall responses assessed by study investigators according to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.

    Time frame: From Randomization to Objective Progression (Up to 28 Months)

  4. Pharmacokinetics (PK): Minimum Serum Concentration (Cmin) Before 2nd, 4th, 7th, and 10th Infusion

    PK Cmin of Ramucirumab Blood samples were collected at specified time points, and in the event of an infusion-related reaction, for assessment of ramucirumab serum concentrations.

    Time frame: Predose, Weeks 2, 6, 12 and 18, Day 1; Up to 3 Days Before Infusion (14-Day Cycles)

  5. PK: Serum Concentration Maximum (Cmax) After 1st, 2nd, 4th, 7th and 10th Ram Infusion

    PK Cmax of Ramucirumab Blood samples were collected at specified time points, and in the event of an infusion-related reaction, for assessment of ramucirumab serum concentrations.

    Time frame: Weeks 0, 2, 6, 12 and 18, Day 1; 1 hour to 1.5 hours Post End of Infusion (14 day-Cycles)

  6. Percentage of Participants With Anti-Ramucirumab Antibodies

    Percentage of participants with positive treatment emergent anti-drug antibodies was summarized by treatment group. A treatment-emergent ADA (TEADA) was defined as: having a negative ADA at baseline and an ADA titer greater than or equal to 1:20 (that is (i.e.), greater than 2-fold from the minimal required dilution of 1:10) any time post baseline (i.e., treatment-induced); or a 4-fold or greater change in ADA titer from baseline for participants that had a detectable ADA titer at baseline (i.e., treatment boosted).

    Time frame: Predose Cycle 1: 7 Days prior to First Infusion, Cycle 4: 3 Days Prior to Infusion, Cycle 7 through Follow Up (Up to 28 Months)

  7. Time to Deterioration of Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8)

    The FACT Hepatobiliary Symptom Index (FHSI-8) is a instrument with specific focus regarding the most frequent and concerning symptoms experienced by participants with hepatobiliary malignancies, including lack of energy, nausea, pain, weight loss, pain in back, fatigue, jaundice, stomach pain or discomfort. The (FHSI-8) questionnaire was used to assess the time to deterioration of FSHI-8 total score issued from the date of randomization to the first date observing deterioration, with the deterioration threshold defined as a decrease ≥ 3-points from baseline. In case of no deterioration, the participants were censored at the time of the last FSHI-8 item recording. FHSI-8 total score ranges from 0 to 32 where "0" is a severely symptomatic participant and the highest score indicates an asymptomatic participant. Kaplan-Meier method Hazard ratio was used to estimate (Ramucirumab versus Placebo) and 95% Confidence Interval (CI) (Wald) were estimated from un-stratified/stratified Cox model.

    Time frame: From Randomization to the First Date of Deterioration Observation (≥ 3-point decrease) (Up to 28 Months)

  8. Change From Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire

    The EQ-5D-5L is a nonspecific and standardized instrument for use as a measure of self-reported health status (EuroQol Group 1990; Herdman et al. 2011). Participants completed the 5-level (no problems, slight problems, moderate problems, severe problems, and extreme problems), 5-dimension (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) questionnaire concerning their current health state. A unique EQ-5D-5L health state scale ranges from 0 to 100 and is defined by combining 1 level from each of the 5 dimensions. Participants indicated their current health status by marking on a continuum ranging from 100 (best imaginable health state) to 0 (worst imaginable health state).

    Time frame: From Randomization through End of Study (Up to 28 Months)

  9. Time to Deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS)

    Time to deterioration in ECOG PS is defined as the time from the date of randomization to the first date observing ECOG PS 2 (ie, deterioration from baseline status of 0 \[fully active\] or 1 \[restricted in physically strenuous activity but ambulatory and able to carry out light work\]). Participants without PS deterioration were censored at their last documented assessments of 0 or 1. Assessments included ECOG Performance Status (PS): 2- Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours, 3 -Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours, 4 -Completely disabled, cannot carry on any self-care. Totally confined to bed or chair, 5- Dead.

    Time frame: From Randomization through First Date of Deterioration Observation (ECOG PS≥2) (Up to 28 Months)

07

Results

Posted May 17, 2019

Participant flow

1. Main study: Participants who received sorafenib as first-line therapy were randomized to ramucirumab or placebo. 2. Open-Label Expansion: Participants who were not previously treated with sorafenib were enrolled into this single-arm addenda and treated with ramucirumab. The purpose of this addenda is to monitor safety, and data was reported under AE section. (Continued...)

Participant flow — Overall Study
MilestoneRamucirumab + BSCPlacebo + BSCOpen Label Ramucirumab + BSCRamucirumab MEE CohortPlacebo MEE Cohort
Started19795473921
Participants who received study drug19795473921
Completed19390423821
Not completed45510
Withdrew: Withdrawal by subject23100
Withdrew: Lost to follow-up22410

Outcome measures

PrimaryOverall Survival (OS)

OS time was measured from date of randomization to date of death from any cause. Participants who were not known to have died on or before the date of data cut-off, OS data was censored on the last date (on or before the cut-off date) the participant was known to be alive.

Time frame:
From Date of Randomization to Death from Any Cause (Up to 28 Months)
Reported as:
Median · Months
Overall Survival (OS)
MonthsRamucirumab + Best Supportive Care (BSC)Placebo + BSC
Overall Survival (OS)8.51 (7.00 to 10.58)7.29 (5.42 to 9.07)
Statistical analysis
  • Ramucirumab + Best Supportive Care (BSC) vs Placebo + BSC · Log Rank · p = 0.0199 · Hazard ratio (hr): 0.710 · 95% CI 0.531 to 0.949Stratified analysis
SecondaryProgression Free Survival (PFS)

Progression-free survival is defined as time from the date of randomization to the date of first observation of objective progression or death from any cause.

Time frame:
From Randomization to Objective Progression or Death from Any Cause (Up to 28 Months)
Reported as:
Median · Months
Progression Free Survival (PFS)
MonthsRamucirumab + BSCPlacebo + BSC
Progression Free Survival (PFS)2.83 (2.76 to 4.11)1.61 (1.45 to 2.69)
Statistical analysis
  • Ramucirumab + BSC vs Placebo + BSC · Log Rank · p = <0.0001 · Hazard ratio (hr): 0.452 · 95% CI 0.339 to 0.603Stratified analysis
SecondaryTime to Radiographic Progression

Time to radiographic progression is defined as the time from the date of randomization to the date of first observation of objective progression.

Time frame:
From Randomization to Objective Progression (Up to 28 Months)
Reported as:
Median · Months
Time to Radiographic Progression
MonthsRamucirumab + BSCPlacebo + BSC
Time to Radiographic Progression3.02 (2.79 to 4.17)1.61 (1.45 to 2.73)
Statistical analysis
  • Ramucirumab + BSC vs Placebo + BSC · Log Rank · p = <0.0001 · Hazard ratio (hr): 0.427 · 95% CI 0.313 to 0.582Stratified analysis
SecondaryPercentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)

Objective response rate is defined as the percentage of participants who achieve a best overall response of complete response (CR) + partial response (PR). ORR = CR + PR. CR is the disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Tumor marker results must have normalized. Best overall response is classified based on the overall responses assessed by study investigators according to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.

Time frame:
From Randomization to Objective Progression (Up to 28 Months)
Reported as:
Number · percentage of participants
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)
percentage of participantsRamucirumab + BSCPlacebo + BSC
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)4.61.1
Statistical analysis
  • Ramucirumab + BSC vs Placebo + BSC · Cochran-Mantel-Haenszel · p = 0.1697 · Odds ratio (or): 4.6 · 95% CI 0.6 to 37.3Stratified analysis
SecondaryPharmacokinetics (PK): Minimum Serum Concentration (Cmin) Before 2nd, 4th, 7th, and 10th Infusion

PK Cmin of Ramucirumab Blood samples were collected at specified time points, and in the event of an infusion-related reaction, for assessment of ramucirumab serum concentrations.

Time frame:
Predose, Weeks 2, 6, 12 and 18, Day 1; Up to 3 Days Before Infusion (14-Day Cycles)
Reported as:
Geometric mean · nanogram/milliliter (ng/mL)
Pharmacokinetics (PK): Minimum Serum Concentration (Cmin) Before 2nd, 4th, 7th, and 10th Infusion
nanogram/milliliter (ng/mL)Ramucirumab + BSC
Week 0NA ± NA
Week 223.5 ± 57
Week 644.1 ± 60
Week 1260.2 ± 46
Week 1863.2 ± 40
SecondaryPK: Serum Concentration Maximum (Cmax) After 1st, 2nd, 4th, 7th and 10th Ram Infusion

PK Cmax of Ramucirumab Blood samples were collected at specified time points, and in the event of an infusion-related reaction, for assessment of ramucirumab serum concentrations.

Time frame:
Weeks 0, 2, 6, 12 and 18, Day 1; 1 hour to 1.5 hours Post End of Infusion (14 day-Cycles)
Reported as:
Geometric mean · ng/mL
PK: Serum Concentration Maximum (Cmax) After 1st, 2nd, 4th, 7th and 10th Ram Infusion
ng/mLRamucirumab + BSC
Week 0156 ± 22
Week 2181 ± 24
Week 6205 ± 24
Week 12221 ± 24
Week 18228 ± 22
SecondaryPercentage of Participants With Anti-Ramucirumab Antibodies

Percentage of participants with positive treatment emergent anti-drug antibodies was summarized by treatment group. A treatment-emergent ADA (TEADA) was defined as: having a negative ADA at baseline and an ADA titer greater than or equal to 1:20 (that is (i.e.), greater than 2-fold from the minimal required dilution of 1:10) any time post baseline (i.e., treatment-induced); or a 4-fold or greater change in ADA titer from baseline for participants that had a detectable ADA titer at baseline (i.e., treatment boosted).

Time frame:
Predose Cycle 1: 7 Days prior to First Infusion, Cycle 4: 3 Days Prior to Infusion, Cycle 7 through Follow Up (Up to 28 Months)
Reported as:
Number · percentage of participants
Percentage of Participants With Anti-Ramucirumab Antibodies
percentage of participantsRamucirumab + BSCPlacebo + BSC
Percentage of Participants With Anti-Ramucirumab Antibodies5.09.2
SecondaryTime to Deterioration of Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8)

The FACT Hepatobiliary Symptom Index (FHSI-8) is a instrument with specific focus regarding the most frequent and concerning symptoms experienced by participants with hepatobiliary malignancies, including lack of energy, nausea, pain, weight loss, pain in back, fatigue, jaundice, stomach pain or discomfort. The (FHSI-8) questionnaire was used to assess the time to deterioration of FSHI-8 total score issued from the date of randomization to the first date observing deterioration, with the deterioration threshold defined as a decrease ≥ 3-points from baseline. In case of no deterioration, the participants were censored at the time of the last FSHI-8 item recording. FHSI-8 total score ranges from 0 to 32 where "0" is a severely symptomatic participant and the highest score indicates an asymptomatic participant. Kaplan-Meier method Hazard ratio was used to estimate (Ramucirumab versus Placebo) and 95% Confidence Interval (CI) (Wald) were estimated from un-stratified/stratified Cox model.

Time frame:
From Randomization to the First Date of Deterioration Observation (≥ 3-point decrease) (Up to 28 Months)
Reported as:
Median · Months
Time to Deterioration of Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8)
MonthsRamucirumab + BSCPlacebo + BSC
Time to Deterioration of Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8)3.71 (2.79 to 4.40)2.79 (1.64 to 2.89)
Statistical analysis
  • Ramucirumab + BSC vs Placebo + BSC · Log Rank · p = 0.2382 · Hazard ratio (hr): 0.799 · 95% CI 0.545 to 1.171Stratified analysis
SecondaryChange From Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire

The EQ-5D-5L is a nonspecific and standardized instrument for use as a measure of self-reported health status (EuroQol Group 1990; Herdman et al. 2011). Participants completed the 5-level (no problems, slight problems, moderate problems, severe problems, and extreme problems), 5-dimension (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) questionnaire concerning their current health state. A unique EQ-5D-5L health state scale ranges from 0 to 100 and is defined by combining 1 level from each of the 5 dimensions. Participants indicated their current health status by marking on a continuum ranging from 100 (best imaginable health state) to 0 (worst imaginable health state).

Time frame:
From Randomization through End of Study (Up to 28 Months)
Reported as:
Mean · units on a scale
Change From Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire
units on a scaleRamucirumab + BSCPlacebo + BSC
Change From Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire-0.105 ± 0.201-0.099 ± 0.170
SecondaryTime to Deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS)

Time to deterioration in ECOG PS is defined as the time from the date of randomization to the first date observing ECOG PS 2 (ie, deterioration from baseline status of 0 \[fully active\] or 1 \[restricted in physically strenuous activity but ambulatory and able to carry out light work\]). Participants without PS deterioration were censored at their last documented assessments of 0 or 1. Assessments included ECOG Performance Status (PS): 2- Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours, 3 -Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours, 4 -Completely disabled, cannot carry on any self-care. Totally confined to bed or chair, 5- Dead.

Time frame:
From Randomization through First Date of Deterioration Observation (ECOG PS≥2) (Up to 28 Months)
Reported as:
Median · Months
Time to Deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
MonthsRamucirumab + BSCPlacebo + BSC
Time to Deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS)NA (9.33 to NA)NA (5.26 to NA)

Adverse events

Collected over Baseline up to 3.2 years. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Ramucirumab + BSC162/197 (82.2%)72/197 (36.5%)189/197 (95.9%)
Placebo+BSC76/95 (80%)27/95 (28.4%)77/95 (81.1%)
Open Label Ramucirumab + BSC33/47 (70.2%)18/47 (38.3%)40/47 (85.1%)
Ramucirumab MEE Cohort35/39 (89.7%)10/39 (25.6%)39/39 (100%)
Placebo MEE Cohort18/21 (85.7%)3/21 (14.3%)17/21 (81%)
Most frequent serious events
Showing 10 of 107
Most frequent serious events
EventRamucirumab + BSCPlacebo+BSCOpen Label Ramucirumab + BSCRamucirumab MEE CohortPlacebo MEE Cohort
Upper gastrointestinal haemorrhageGastrointestinal disorders1/1970/951/473/390/21
PneumoniaInfections and infestations5/1973/952/472/390/21
Hepatic function abnormalHepatobiliary disorders0/1970/950/470/391/21
Abdominal infectionInfections and infestations0/1970/950/470/391/21
Hepatic encephalopathyNervous system disorders3/1970/950/470/391/21
PyrexiaGeneral disorders3/1971/952/470/390/21
SepsisInfections and infestations3/1973/950/470/390/21
AscitesGastrointestinal disorders6/1970/951/470/390/21
AnaemiaBlood and lymphatic system disorders0/1970/951/471/390/21
Gastrointestinal haemorrhageGastrointestinal disorders0/1971/951/471/390/21
Most frequent other events
Showing 10 of 63
Most frequent other events
EventRamucirumab + BSCPlacebo+BSCOpen Label Ramucirumab + BSCRamucirumab MEE CohortPlacebo MEE Cohort
Aspartate aminotransferase increasedInvestigations16/19710/953/4715/397/21
Platelet count decreasedInvestigations23/1972/956/4714/390/21
HypoalbuminaemiaMetabolism and nutrition disorders21/1974/954/4714/394/21
Blood bilirubin increasedInvestigations21/1978/955/4711/396/21
FatigueGeneral disorders54/19716/957/471/392/21
Oedema peripheralGeneral disorders52/19713/957/476/392/21
ProteinuriaRenal and urinary disorders43/1974/9512/4710/390/21
HypertensionVascular disorders50/19712/9511/477/392/21
Decreased appetiteMetabolism and nutrition disorders49/19719/956/473/395/21
Alanine aminotransferase increasedInvestigations7/1975/952/478/395/21

Baseline characteristics

All participants who received at least one dose of study drug.

Age, Continuous
Age, Continuous(years)Ramucirumab + BSCPlacebo + Best Supportive Care (BSC)Open Label Ramucirumab + BSCRamucirumab MEE CohortPlacebo MEE CohortTotal
Median64 (30 to 88)64 (26 to 85)61 (36 to 82)54 (24 to 74)54 (31 to 66)62 (24 to 88)
Sex: Female, Male
Sex: Female, Male(Participants)Ramucirumab + BSCPlacebo + Best Supportive Care (BSC)Open Label Ramucirumab + BSCRamucirumab MEE CohortPlacebo MEE CohortTotal
Female431667173
Male15479413220326
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Ramucirumab + BSCPlacebo + Best Supportive Care (BSC)Open Label Ramucirumab + BSCRamucirumab MEE CohortPlacebo MEE CohortTotal
Hispanic or Latino12910022
Not Hispanic or Latino1295840129248
Unknown or Not Reported562862712129
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Ramucirumab + BSCPlacebo + Best Supportive Care (BSC)Open Label Ramucirumab + BSCRamucirumab MEE CohortPlacebo MEE CohortTotal
American Indian or Alaska Native000000
Asian10245263921233
Native Hawaiian or Other Pacific Islander000000
Black or African American114006
White60311300104
More than one race014005
Unknown or Not Reported341700051
Region of Enrollment
Region of Enrollment(Participants)Ramucirumab + BSCPlacebo + Best Supportive Care (BSC)Open Label Ramucirumab + BSCRamucirumab MEE CohortPlacebo MEE CohortTotal
Hong Kong6180015
United States101120023
Czechia420006
Japan411800059
United Kingdom9200011
Switzerland221005
Spain320005
Canada110002
Austria110002
South Korea241400038
Belgium220004
China318392172
Taiwan2211100043
Brazil540009
Poland230005
Italy13900022
Israel100001
Australia210003
France341700051
Germany12380023
08

Study locations

131 sites
  • Pacific Hematology and Oncology Associates
    Daly City, California 94115, United States
  • UCLA Medical Center
    Los Angeles, California 90024, United States
  • Georgetown University Medical Center
    Washington D.C., District of Columbia 20007, United States
  • University of Iowa Hospital
    Iowa City, Iowa 52242, United States
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
  • Mount Sinai Medical Center
    New York, New York 10029, United States
  • University of Oklahoma Health Sciences Center
    Oklahoma City, Oklahoma 73104, United States
  • OREGON HEALTH and SCIENCE UNIVERSITY
    Portland, Oregon 97239, United States
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    Kurralta Park, 5037, Australia
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    Woodville, 5011, Australia
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    Linz, 4020, Austria
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    Vienna, 1090, Austria
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    Brussels, 1200, Belgium
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    Liège, 4000, Belgium
  • Fundação PIO XII
    Barretos, 14784-400, Brazil
  • "For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician."
    Barretos, 14784700, Brazil
  • Cenantron - Centro Avançado de Tratamento Oncológico
    Belo Horizonte, 30130-090, Brazil
  • Associação Hospital de Caridade Ijuí
    Ijuí, 98700 000, Brazil
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    Porto Alegre, 90470-340, Brazil
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    São Paulo, 04039-901, Brazil
  • For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
    Montreal, H2X 3E4, Canada
  • For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
    Toronto, M5G 2M9, Canada
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    Beijing, 100032, China
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    Beijing, 100142, China
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    Beijing, China
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    Beijing, China
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    Changsha, 410011, China
  • "For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician."
    Changsha, 410013, China
  • "For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician."
    Chongqing, 400038, China
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    Guangdong, 510515, China
  • "For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician."
    Guangzhou, 510080, China
  • "For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician."
    Hangzhou, 310003, China
  • "For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician."
    Hangzhou, 310009, China
  • "For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician."
    Hangzhou, 310022, China
  • "For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician."
    Hebei, 050011, China
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    Hefei, 230022, China
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    Heilongjiang, 150081, China
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    Henan, 450008, China
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    Hubei, 56456, China
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    Nanjing, 210002, China
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    Nanjing, 210006, China
  • "For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician."
    Nanning, 530021, China
  • "For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician."
    Qingdao, 266003, China
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    Shanghai, 200030, China
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
    Shanghai, 200127, China
  • "For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician."
    Shanghai, China
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    Shanghai, China
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    Shenyang, 100042, China
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    Wuhan, 430030, China
  • "For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician."
    Xi'an, 710032, China
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    Brno, 656 53, Czechia
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    Prague, 150 06, Czechia
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    Amiens, 80054, France
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    Avignon, 84918, France
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    Besançon, 25030, France
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    Caen, 14033, France
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    Clermont-Ferrand, 63003, France
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    Lyon, 69317, France
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    Montpellier, 34295, France
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    Nantes, 44093, France
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    Pessac, 33604, France
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    Rennes, 35042, France
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    Saint-Etienne, 42000, France
  • "For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician."
    Bayern, 81377, Germany
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    Berlin, 13125, Germany
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    Essen, 45122, Germany
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    Frankfurt, 60590, Germany
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    Hamburg, 20246, Germany
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    Hanover, 30625, Germany
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    Leipzig, 04103, Germany
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    Magdeburg, 39120, Germany
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    Mainz, 55131, Germany
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    München, 81675, Germany
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    Tübingen, 72076, Germany
  • "For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician."
    Hong Kong, Hong Kong
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    Hong Kong, Hong Kong
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    Kowloon, Hong Kong
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    Shatin, Hong Kong
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    Tuenmen, Hong Kong
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    Haifa, 3109601, Israel
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    Tel Aviv, 6423906, Israel
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    Benevento, 82100, Italy
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    Bologna, 40138, Italy
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    Cremona, 26100, Italy
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    Padova, 35128, Italy
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    Rome, 00168, Italy
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    Chūōku, 104-0045, Japan
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    Fukuoka, 810-8563, Japan
  • "For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician."
    Fukuoka, 811-1395, Japan
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    Iizuka, 820-8505, Japan
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    Kanazawa, 920-8641, Japan
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    Kashiwa, 277 8577, Japan
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    Kyoto, 606-8507, Japan
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    Matsuyama, 791-0280, Japan
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    Osaka, 589-8511, Japan
  • "For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician."
    Ōsaka, 541-8567, Japan
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    Shimotsuke, 329-0498, Japan
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    Suita-shi, 565-0871, Japan
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    Sunto-Gun, 411-8777, Japan
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    Tokyo, 101-0062, Japan

Showing the first 100 of 131 sites across 20 countries.

09

References and documents

Publications

  • Shao G, Bai Y, Yuan X, Chen X, Gu S, Gu K, Hu C, Liang H, Guo Y, Wang J, Yen CJ, Lee VH, Wang C, Widau RC, Zhang W, Liu J, Zhang Q, Qin S. Ramucirumab as second-line treatment in Chinese patients with advanced hepatocellular carcinoma and elevated alpha-fetoprotein after sorafenib (REACH-2 China): A randomised, multicentre, double-blind study. EClinicalMedicine. 2022 Oct 6;54:101679. doi: 10.1016/j.eclinm.2022.101679. eCollection 2022 Dec. PubMed 36247923 ↗
  • 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. PubMed 35247922 ↗
  • 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. PubMed 34795131 ↗
  • Trojan J, Mollon P, Daniele B, Marteau F, Martin L, Li Y, Xu Q, Piscaglia F, Zaucha R, Sarker D, Lim HY, Venerito M. Comparative Efficacy of Cabozantinib and Ramucirumab After Sorafenib for Patients with Hepatocellular Carcinoma and Alpha-fetoprotein >/= 400 ng/mL: A Matching-Adjusted Indirect Comparison. Adv Ther. 2021 May;38(5):2472-2490. doi: 10.1007/s12325-021-01700-2. Epub 2021 Apr 6. PubMed 33822328 ↗
  • 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. PubMed 33531690 ↗
  • 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. PubMed 33188713 ↗
  • 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. PubMed 32817068 ↗
  • 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. PubMed 32107609 ↗
  • Zhu AX, Kang YK, Yen CJ, Finn RS, Galle PR, Llovet JM, Assenat E, Brandi G, Pracht M, Lim HY, Rau KM, Motomura K, Ohno I, Merle P, Daniele B, Shin DB, Gerken G, Borg C, Hiriart JB, Okusaka T, Morimoto M, Hsu Y, Abada PB, Kudo M; REACH-2 study investigators. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased alpha-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Feb;20(2):282-296. doi: 10.1016/S1470-2045(18)30937-9. Epub 2019 Jan 18. PubMed 30665869 ↗

Study documents

  • Study protocol · Apr 24, 2017
  • Statistical analysis plan · Dec 21, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Supporting information: Study protocol, Statistical analysis plan, Clinical study report

Time frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.

Access criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Data sharing details ↗ · www.clinicalstudydatarequest.com

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Jul 2015 to primary completion in Mar 2018, 31 months.

Results were first posted in May 2019, 1 year 2 months after primary completion.

Of 47 industry-sponsored phase 3 interventional studies under Carcinoma, Hepatocellular, half reached primary completion within 51 months of starting (the median), counting those still running; a quarter within 41 and three quarters within 63. This study's 31 months is below that.

Counting every sponsor, half of 130 studies reached it within 57 months; a quarter within 44 and three quarters within 83.

How these figures are worked out, and which studies are left out of them.

Registered
May 1, 2015
First posted
May 6, 2015
StartActual
Jul 20, 2015
Primary completionActual
Mar 15, 2018
CompletionActual
Nov 19, 2021
Results first posted
May 17, 2019
Last update
Jan 20, 2023
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jan 20, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02435433
Lead sponsor
Eli Lilly and Company
Responsible party
Sponsor
First posted
May 6, 2015
Start date
Jul 20, 2015
Primary completion
Mar 15, 2018
Completion
Nov 19, 2021
Results posted
May 17, 2019
Last update
Jan 20, 2023

Study contacts

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)
study director · Eli Lilly and Company

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Dec 2022. You cannot join it, but the record below documents what was studied.

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Discussion

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Studies of the drug tested here: Ramucirumab

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