Trial Outcomes & Findings for Study of IMC-1121B (Ramucirumab) in Participants With Liver Cancer Who Have Not Previously Been Treated With Chemotherapy (NCT NCT00627042)
NCT ID: NCT00627042
Last Updated: 2014-10-08
Results Overview
PFS was defined as the time from the first day of therapy to the first evidence of disease progression or death from any cause. As classified according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria, disease progression was having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of a new lesion. Participants who were alive and without disease progression and participants who did not progress and were subsequently lost to follow-up were censored at the last objective tumor assessment.
COMPLETED
PHASE2
42 participants
First dose to date of progressive disease or death due to any cause [every 3 cycles up to 18 months (1 cycle=2 weeks)]
2014-10-08
Participant Flow
Participant milestones
| Measure |
Ramucirumab (IMC-1121B)
Ramucirumab (IMC-1121B): 8 milligrams per kilogram (mg/kg) administered intravenously over 1 hour, every 2 weeks. Treatment continued until there was evidence of disease progression, intolerable toxicity, or other withdrawal criteria were met.
|
|---|---|
|
Overall Study
STARTED
|
42
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
42
|
|
Overall Study
COMPLETED
|
40
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Ramucirumab (IMC-1121B)
Ramucirumab (IMC-1121B): 8 milligrams per kilogram (mg/kg) administered intravenously over 1 hour, every 2 weeks. Treatment continued until there was evidence of disease progression, intolerable toxicity, or other withdrawal criteria were met.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
Baseline Characteristics
Study of IMC-1121B (Ramucirumab) in Participants With Liver Cancer Who Have Not Previously Been Treated With Chemotherapy
Baseline characteristics by cohort
| Measure |
Ramucirumab (IMC-1121B)
n=42 Participants
Ramucirumab (IMC-1121B): 8 milligrams per kilogram (mg/kg) administered intravenously over 1 hour, every 2 weeks. Treatment continued until there was evidence of disease progression, intolerable toxicity, or other withdrawal criteria were met.
|
|---|---|
|
Age, Customized
Between 18 and 65 years
|
27 participants
10.70 • n=5 Participants
|
|
Age, Customized
>=65 years
|
15 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
34 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
39 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
4 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
2 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
32 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race Other: Hispanic
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race Other: Black and Asian
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race Other: Greek
|
1 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
42 participants
n=5 Participants
|
|
Child-Pugh Score
A
|
31 participants
n=5 Participants
|
|
Child-Pugh Score
B
|
11 participants
n=5 Participants
|
|
Barcelona Stage
A
|
2 participants
n=5 Participants
|
|
Barcelona Stage
B
|
4 participants
n=5 Participants
|
|
Barcelona Stage
C
|
36 participants
n=5 Participants
|
|
Macrovascular Invasion
Present
|
7 participants
n=5 Participants
|
|
Macrovascular Invasion
Absent
|
32 participants
n=5 Participants
|
|
Macrovascular Invasion
Not Available
|
2 participants
n=5 Participants
|
|
Macrovascular Invasion
Missing
|
1 participants
n=5 Participants
|
|
Extrahepatic Metastasis Status
Present
|
32 participants
n=5 Participants
|
|
Extrahepatic Metastasis Status
Absent
|
10 participants
n=5 Participants
|
|
Hepatitis B and C Status
Hepatitis B Positive
|
3 participants
n=5 Participants
|
|
Hepatitis B and C Status
Hepatitis C Positive
|
19 participants
n=5 Participants
|
|
Hepatitis B and C Status
Hepatitis B and C Positive
|
2 participants
n=5 Participants
|
|
Hepatitis B and C Status
Hepatitis B and C Negative
|
15 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: First dose to date of progressive disease or death due to any cause [every 3 cycles up to 18 months (1 cycle=2 weeks)]Population: Intent-to-treat population: Participants who received at least 1 dose of ramucirumab. The number of participants censored was 13.
PFS was defined as the time from the first day of therapy to the first evidence of disease progression or death from any cause. As classified according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria, disease progression was having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of a new lesion. Participants who were alive and without disease progression and participants who did not progress and were subsequently lost to follow-up were censored at the last objective tumor assessment.
Outcome measures
| Measure |
Ramucirumab (IMC-1121B)
n=42 Participants
Ramucirumab (IMC-1121B): 8 milligrams per kilogram (mg/kg) administered intravenously over 1 hour, every 2 weeks. Treatment continued until there was evidence of disease progression, intolerable toxicity, or other withdrawal criteria were met.
|
|---|---|
|
Progression Free Survival (PFS) in Participants With Unresectable Hepatocellular Cancer Treated With the Monoclonal Antibody Ramucirumab
|
4.0 months
Interval 2.6 to 5.7
|
SECONDARY outcome
Timeframe: First dose to date of PD [every 3 cycles up to 18 months (1 cycle=2 weeks)]Population: Intent-to-treat population: Participants who received at least 1 dose of ramucirumab. The number of participants censored was 20.
The time from first day of therapy to the first date of objective evidence of progressive disease (PD) by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD was defined as having at least a 20% increase in sum of longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of new lesion. Time to PD was censored at the date of death or study discontinuation.
Outcome measures
| Measure |
Ramucirumab (IMC-1121B)
n=42 Participants
Ramucirumab (IMC-1121B): 8 milligrams per kilogram (mg/kg) administered intravenously over 1 hour, every 2 weeks. Treatment continued until there was evidence of disease progression, intolerable toxicity, or other withdrawal criteria were met.
|
|---|---|
|
Time to Progression
|
4.2 months
Interval 2.8 to 8.4
|
SECONDARY outcome
Timeframe: First dose to death due to any cause up to 37.5 monthsPopulation: Intent-to-treat population: Participants who received at least 1 dose of ramucirumab. The number of participants censored was 10.
Overall survival (OS) was the duration from first dose to death due to any cause. OS was censored at last contact date for participants who were alive at the end of follow-up period or lost to follow-up.
Outcome measures
| Measure |
Ramucirumab (IMC-1121B)
n=42 Participants
Ramucirumab (IMC-1121B): 8 milligrams per kilogram (mg/kg) administered intravenously over 1 hour, every 2 weeks. Treatment continued until there was evidence of disease progression, intolerable toxicity, or other withdrawal criteria were met.
|
|---|---|
|
Overall Survival
|
12.0 months
Interval 6.1 to 19.7
|
SECONDARY outcome
Timeframe: First dose to date of objective progressive disease (PD) or death up to 18 monthsPopulation: Intent-to-treat population: Participants who received at least 1 dose of ramucirumab.
Objective response rate (ORR) was defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR). As classified according to Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria, CR was the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeters (mm) and normalization of tumor marker level of non-target lesions. PR was having at least a 30% decrease in sum of longest diameter of target lesions.
Outcome measures
| Measure |
Ramucirumab (IMC-1121B)
n=42 Participants
Ramucirumab (IMC-1121B): 8 milligrams per kilogram (mg/kg) administered intravenously over 1 hour, every 2 weeks. Treatment continued until there was evidence of disease progression, intolerable toxicity, or other withdrawal criteria were met.
|
|---|---|
|
Percentage of Participants With Complete Response or Partial Response (Objective Response Rate)
|
9.5 percentage of participants
Interval 2.7 to 22.6
|
SECONDARY outcome
Timeframe: Time of first response (CR or PR) to disease progression, or death due to any cause [every 3 cycles up to 18 months (1 cycle=2 weeks)]Population: Participants who received at least 1 dose of ramucirumab and had a CR or PR. The number of participants censored 2.
Duration of response was the interval from the date of initial documented response \[complete response (CR) or partial response (PR)\] to the first documented date of disease progression, initiation of other (or additional) antitumor therapy was first reported, or death due to any cause. As classified according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria, CR was the disappearance of all target lesions, PR was having at least a 30% decrease in the sum of the longest diameter of target lesions, and disease progression was having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of a new lesion. Data were censored for participants who did not progress or die.
Outcome measures
| Measure |
Ramucirumab (IMC-1121B)
n=4 Participants
Ramucirumab (IMC-1121B): 8 milligrams per kilogram (mg/kg) administered intravenously over 1 hour, every 2 weeks. Treatment continued until there was evidence of disease progression, intolerable toxicity, or other withdrawal criteria were met.
|
|---|---|
|
Duration of Response
|
14.1 months
Interval 4.3 to 14.1
|
SECONDARY outcome
Timeframe: Prior to dosing at baseline, Cycles 4 and 7, and 30 days after end of therapy (1 cycle=2 weeks)Population: Intent-to-treat population: Participants who received at least 1 dose of ramucirumab.
Outcome measures
| Measure |
Ramucirumab (IMC-1121B)
n=42 Participants
Ramucirumab (IMC-1121B): 8 milligrams per kilogram (mg/kg) administered intravenously over 1 hour, every 2 weeks. Treatment continued until there was evidence of disease progression, intolerable toxicity, or other withdrawal criteria were met.
|
|---|---|
|
Number of Participants With Serum Anti-Ramucirumab Antibodies
|
6 participants
|
SECONDARY outcome
Timeframe: First dose to 37.5 monthsPopulation: Intent-to-treat population: Participants who received at least 1 dose of ramucirumab.
Data presented are the number of participants who experienced treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), Grade 3 or higher TEAEs, or adverse events (AEs) leading to discontinuation of treatment that were considered by the investigator to be related to ramucirumab. A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.
Outcome measures
| Measure |
Ramucirumab (IMC-1121B)
n=42 Participants
Ramucirumab (IMC-1121B): 8 milligrams per kilogram (mg/kg) administered intravenously over 1 hour, every 2 weeks. Treatment continued until there was evidence of disease progression, intolerable toxicity, or other withdrawal criteria were met.
|
|---|---|
|
Number of Participants With Drug-Related Treatment-Emergent Adverse Events
Related TEAE
|
41 participants
|
|
Number of Participants With Drug-Related Treatment-Emergent Adverse Events
Related SAE
|
9 participants
|
|
Number of Participants With Drug-Related Treatment-Emergent Adverse Events
Related Grade 3 or higher TEAE
|
14 participants
|
|
Number of Participants With Drug-Related Treatment-Emergent Adverse Events
Related AE leading to discontinuation
|
6 participants
|
Adverse Events
Ramucirumab (IMC-1121B)
Serious adverse events
| Measure |
Ramucirumab (IMC-1121B)
n=42 participants at risk
Ramucirumab (IMC-1121B): 8 milligrams per kilogram (mg/kg) administered intravenously over 1 hour, every 2 weeks. Treatment continued until there was evidence of disease progression, intolerable toxicity, or other withdrawal criteria were met.
|
|---|---|
|
Endocrine disorders
ADRENAL INSUFFICIENCY
|
2.4%
1/42 • Number of events 1
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
2.4%
1/42 • Number of events 1
|
|
Gastrointestinal disorders
ASCITES
|
4.8%
2/42 • Number of events 2
|
|
Gastrointestinal disorders
CONSTIPATION
|
2.4%
1/42 • Number of events 1
|
|
Gastrointestinal disorders
GASTROINTESTINAL HAEMORRHAGE
|
7.1%
3/42 • Number of events 3
|
|
Gastrointestinal disorders
INTESTINAL OBSTRUCTION
|
2.4%
1/42 • Number of events 1
|
|
General disorders
CHILLS
|
2.4%
1/42 • Number of events 1
|
|
General disorders
DISEASE PROGRESSION
|
2.4%
1/42 • Number of events 1
|
|
General disorders
FATIGUE
|
4.8%
2/42 • Number of events 2
|
|
General disorders
INFUSION RELATED REACTION
|
4.8%
2/42 • Number of events 2
|
|
General disorders
PYREXIA
|
4.8%
2/42 • Number of events 2
|
|
Hepatobiliary disorders
HEPATIC FAILURE
|
2.4%
1/42 • Number of events 1
|
|
Hepatobiliary disorders
HEPATORENAL SYNDROME
|
2.4%
1/42 • Number of events 1
|
|
Immune system disorders
HYPERSENSITIVITY
|
2.4%
1/42 • Number of events 1
|
|
Infections and infestations
BRONCHITIS
|
2.4%
1/42 • Number of events 1
|
|
Infections and infestations
CELLULITIS
|
2.4%
1/42 • Number of events 1
|
|
Infections and infestations
ESCHERICHIA BACTERAEMIA
|
2.4%
1/42 • Number of events 1
|
|
Infections and infestations
PNEUMONIA
|
4.8%
2/42 • Number of events 2
|
|
Infections and infestations
STAPHYLOCOCCAL INFECTION
|
2.4%
1/42 • Number of events 1
|
|
Metabolism and nutrition disorders
ANOREXIA
|
2.4%
1/42 • Number of events 1
|
|
Metabolism and nutrition disorders
FAILURE TO THRIVE
|
2.4%
1/42 • Number of events 1
|
|
Metabolism and nutrition disorders
HYPONATRAEMIA
|
2.4%
1/42 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
2.4%
1/42 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
2.4%
1/42 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
2.4%
1/42 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
HEPATIC NEOPLASM MALIGNANT
|
2.4%
1/42 • Number of events 1
|
|
Nervous system disorders
ENCEPHALOPATHY
|
2.4%
1/42 • Number of events 1
|
|
Nervous system disorders
HEPATIC ENCEPHALOPATHY
|
2.4%
1/42 • Number of events 2
|
|
Nervous system disorders
SYNCOPE
|
2.4%
1/42 • Number of events 1
|
|
Psychiatric disorders
CONFUSIONAL STATE
|
4.8%
2/42 • Number of events 2
|
|
Psychiatric disorders
MENTAL STATUS CHANGES
|
2.4%
1/42 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
HYPOXIA
|
4.8%
2/42 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMONIA ASPIRATION
|
2.4%
1/42 • Number of events 1
|
|
Surgical and medical procedures
HOSPITALISATION
|
2.4%
1/42 • Number of events 1
|
|
Surgical and medical procedures
LIVER TRANSPLANT
|
2.4%
1/42 • Number of events 1
|
|
Vascular disorders
ARTERIOSCLEROSIS
|
2.4%
1/42 • Number of events 1
|
|
Vascular disorders
FEMORAL ARTERY OCCLUSION
|
2.4%
1/42 • Number of events 1
|
|
Vascular disorders
HYPERTENSION
|
7.1%
3/42 • Number of events 3
|
|
Vascular disorders
HYPOTENSION
|
2.4%
1/42 • Number of events 1
|
Other adverse events
| Measure |
Ramucirumab (IMC-1121B)
n=42 participants at risk
Ramucirumab (IMC-1121B): 8 milligrams per kilogram (mg/kg) administered intravenously over 1 hour, every 2 weeks. Treatment continued until there was evidence of disease progression, intolerable toxicity, or other withdrawal criteria were met.
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
EPISTAXIS
|
14.3%
6/42 • Number of events 8
|
|
Vascular disorders
HYPERTENSION
|
38.1%
16/42 • Number of events 18
|
|
Vascular disorders
HYPOTENSION
|
7.1%
3/42 • Number of events 3
|
|
Gastrointestinal disorders
ABDOMINAL DISCOMFORT
|
7.1%
3/42 • Number of events 3
|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
19.0%
8/42 • Number of events 9
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
19.0%
8/42 • Number of events 8
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
16.7%
7/42 • Number of events 8
|
|
Gastrointestinal disorders
ASCITES
|
11.9%
5/42 • Number of events 9
|
|
Gastrointestinal disorders
CONSTIPATION
|
16.7%
7/42 • Number of events 11
|
|
Gastrointestinal disorders
DIARRHOEA
|
33.3%
14/42 • Number of events 22
|
|
Gastrointestinal disorders
DYSPEPSIA
|
7.1%
3/42 • Number of events 3
|
|
Gastrointestinal disorders
GINGIVAL BLEEDING
|
9.5%
4/42 • Number of events 4
|
|
Gastrointestinal disorders
NAUSEA
|
35.7%
15/42 • Number of events 18
|
|
Gastrointestinal disorders
VOMITING
|
11.9%
5/42 • Number of events 5
|
|
General disorders
ASTHENIA
|
7.1%
3/42 • Number of events 3
|
|
General disorders
CHILLS
|
7.1%
3/42 • Number of events 4
|
|
General disorders
FATIGUE
|
66.7%
28/42 • Number of events 37
|
|
General disorders
INFUSION RELATED REACTION
|
11.9%
5/42 • Number of events 7
|
|
General disorders
OEDEMA PERIPHERAL
|
33.3%
14/42 • Number of events 19
|
|
General disorders
PYREXIA
|
7.1%
3/42 • Number of events 3
|
|
Investigations
WEIGHT DECREASED
|
19.0%
8/42 • Number of events 11
|
|
Metabolism and nutrition disorders
ANOREXIA
|
26.2%
11/42 • Number of events 11
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
11.9%
5/42 • Number of events 7
|
|
Metabolism and nutrition disorders
HYPOMAGNESAEMIA
|
9.5%
4/42 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
7.1%
3/42 • Number of events 7
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
9.5%
4/42 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
7.1%
3/42 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
9.5%
4/42 • Number of events 4
|
|
Nervous system disorders
DIZZINESS
|
11.9%
5/42 • Number of events 5
|
|
Nervous system disorders
HEADACHE
|
38.1%
16/42 • Number of events 19
|
|
Nervous system disorders
HYPOAESTHESIA
|
7.1%
3/42 • Number of events 4
|
|
Psychiatric disorders
ANXIETY
|
16.7%
7/42 • Number of events 8
|
|
Psychiatric disorders
INSOMNIA
|
16.7%
7/42 • Number of events 7
|
|
Renal and urinary disorders
RENAL FAILURE
|
7.1%
3/42 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
14.3%
6/42 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
19.0%
8/42 • Number of events 9
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.
- Publication restrictions are in place
Restriction type: OTHER