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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02435433




Registration number
NCT02435433
Ethics application status
Date submitted
1/05/2015
Date registered
6/05/2015

Titles & IDs
Public title
A Study of Ramucirumab (LY3009806) Versus Placebo in Participants With Hepatocellular Carcinoma and Elevated Baseline Alpha-Fetoprotein
Scientific title
Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Ramucirumab and Best Supportive Care (BSC) Versus Placebo and BSC as Second-Line Treatment in Patients With Hepatocellular Carcinoma and Elevated Baseline Alpha-Fetoprotein (AFP) Following First-Line Therapy With Sorafenib
Secondary ID [1] 0 0
I4T-MC-JVDE
Secondary ID [2] 0 0
15755
Universal Trial Number (UTN)
Trial acronym
REACH-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatocellular Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ramucirumab
Treatment: Drugs - Placebo

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.

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

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.

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.

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.


Treatment: Drugs: Ramucirumab
Administered IV

Treatment: Drugs: Placebo
Administered IV
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From Date of Randomization to Death from Any Cause (Up to 28 Months)
Secondary outcome [1] 0 0
Progression Free Survival (PFS)
Timepoint [1] 0 0
From Randomization to Objective Progression or Death from Any Cause (Up to 28 Months)
Secondary outcome [2] 0 0
Time to Radiographic Progression
Timepoint [2] 0 0
From Randomization to Objective Progression (Up to 28 Months)
Secondary outcome [3] 0 0
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)
Timepoint [3] 0 0
From Randomization to Objective Progression (Up to 28 Months)
Secondary outcome [4] 0 0
Pharmacokinetics (PK): Minimum Serum Concentration (Cmin) Before 2nd, 4th, 7th, and 10th Infusion
Timepoint [4] 0 0
Predose, Weeks 2, 6, 12 and 18, Day 1; Up to 3 Days Before Infusion (14-Day Cycles)
Secondary outcome [5] 0 0
PK: Serum Concentration Maximum (Cmax) After 1st, 2nd, 4th, 7th and 10th Ram Infusion
Timepoint [5] 0 0
Weeks 0, 2, 6, 12 and 18, Day 1; 1 hour to 1.5 hours Post End of Infusion (14 day-Cycles)
Secondary outcome [6] 0 0
Percentage of Participants With Anti-Ramucirumab Antibodies
Timepoint [6] 0 0
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)
Secondary outcome [7] 0 0
Time to Deterioration of Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8)
Timepoint [7] 0 0
From Randomization to the First Date of Deterioration Observation (= 3-point decrease) (Up to 28 Months)
Secondary outcome [8] 0 0
Change From Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire
Timepoint [8] 0 0
From Randomization through End of Study (Up to 28 Months)
Secondary outcome [9] 0 0
Time to Deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
Timepoint [9] 0 0
From Randomization through First Date of Deterioration Observation (ECOG PS=2) (Up to 28 Months)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/07/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/11/2021
Sample size
Target
Accrual to date
Final
399
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
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
Recruitment hospital [2] 0 0
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. - Woodville
Recruitment postcode(s) [1] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [2] 0 0
5011 - Woodville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Iowa
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Oklahoma
Country [7] 0 0
United States of America
State/province [7] 0 0
Oregon
Country [8] 0 0
Austria
State/province [8] 0 0
Linz
Country [9] 0 0
Austria
State/province [9] 0 0
Wien
Country [10] 0 0
Belgium
State/province [10] 0 0
Brussels
Country [11] 0 0
Belgium
State/province [11] 0 0
Liege
Country [12] 0 0
Brazil
State/province [12] 0 0
Barretos
Country [13] 0 0
Brazil
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Belo Horizonte
Country [14] 0 0
Brazil
State/province [14] 0 0
Ijui
Country [15] 0 0
Brazil
State/province [15] 0 0
Porto Alegre
Country [16] 0 0
Brazil
State/province [16] 0 0
São Paulo
Country [17] 0 0
Canada
State/province [17] 0 0
Montreal
Country [18] 0 0
Canada
State/province [18] 0 0
Toronto
Country [19] 0 0
China
State/province [19] 0 0
Beijing
Country [20] 0 0
China
State/province [20] 0 0
Changsha
Country [21] 0 0
China
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Chongqing
Country [22] 0 0
China
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Guangdong
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China
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Guangzhou
Country [24] 0 0
China
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Hangzhou
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China
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Hebei
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China
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Hefei
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China
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Heilongjiang
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China
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Henan
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China
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Hubei
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China
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Nanjing
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China
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Nanning
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China
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Qingdao
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China
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Shanghai
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China
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Shenyang
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China
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Wu Han
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China
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Xi'an
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Czechia
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Brno
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Czechia
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Praha 5
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France
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Amiens
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France
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Avignon
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France
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Besancon
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France
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Caen
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France
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Clermont-Ferrand
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France
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Lyon
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France
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Montpellier
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France
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Nantes
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France
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Pessac
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France
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Rennes
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France
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Saint Etienne
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Germany
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Bayern
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Germany
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Berlin
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Germany
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Essen
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Germany
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Frankfurt
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Germany
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Hamburg
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Germany
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Hannover
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Germany
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Leipzig
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Germany
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Magdeburg
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Germany
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Mainz
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Germany
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München
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Germany
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Tubingen
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Hong Kong
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Hong Kong
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Hong Kong
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Kowloon
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Hong Kong
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ShaTin
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Hong Kong
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Tuen Mun
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Israel
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Haifa
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Israel
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Tel Aviv
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Italy
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Benevento
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Italy
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Bologna
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Italy
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Cremona
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Italy
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Padova
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Italy
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Rome
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Japan
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Chuo Ku
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Japan
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Fukuoka
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Japan
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Iizuka
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Japan
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Kanazawa
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Japan
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Kashiwa
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Japan
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Kyoto
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Japan
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Matsuyama
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Japan
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Osaka
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Japan
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Shimotsuke
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Japan
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Suita-shi
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Japan
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Sunto-Gun
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Japan
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Tokyo
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Japan
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Yokohama
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Korea, Republic of
State/province [85] 0 0
Incheon
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Korea, Republic of
State/province [86] 0 0
Seoul
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Korea, Republic of
State/province [87] 0 0
Ulsan
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Poland
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Gdansk
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Poland
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Poznan
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Poland
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Warszawa
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Spain
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Girona
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Spain
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Madrid
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Spain
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Santander
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Spain
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Valencia
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Switzerland
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Bern
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Taiwan
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Kaohsiung city
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Taiwan
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Puzi City
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Taiwan
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Taichung
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Taiwan
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Tainan
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Taiwan
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Taipei city
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Taiwan
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Taoyuan City
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United Kingdom
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Acton
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United Kingdom
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Bebington
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United Kingdom
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Birmingham
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United Kingdom
State/province [105] 0 0
London
Country [106] 0 0
United Kingdom
State/province [106] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
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)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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 document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
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.
Available to whom?
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.clinicalstudydatarequest.com/


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02435433