Trial Outcomes & Findings for Bevacizumab and Erlotinib in Treating Patients With Advanced Liver Cancer (NCT NCT00365391)
NCT ID: NCT00365391
Last Updated: 2015-07-09
Results Overview
Responses to erlotinib and bevacizumab treatment were evaluated using Response Evaluation Criteria In Solid Tumors (RECIST). A Complete Response (CR) is defined as the disappearance of all target lesions. A Partial Response (PR) is defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum of the longest diameters.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
27 participants
Primary outcome timeframe
Patients were able to continue treatment indefinitely and were evaluated every cycle until discontinued treatment.
Results posted on
2015-07-09
Participant Flow
Between October 2006 and March 2008, 27 patients with advanced hepatocellular carcinoma (HCC) were accrued onto the study.
Participant milestones
| Measure |
Treatment (Bevacizumab and Erlotinib)
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory studies to determine epidermal growth factor receptor (EGFR) and phosphorylated-EGFR protein levels using initial diagnostic biopsy specimens by immuno-histochemistry (IHC) for correlation with clinical outcome. Levels of proteins through which EGFR signals, including Akt, phosphorylated-Akt, mitogen-activated protein kinase (MAPK), and phosphorylated-MAPK, are also determined using initial diagnostic biopsy specimens by IHC and correlated with clinical outcome. Total and free serum vascular endothelial growth factor levels are determined at the start of study and prior to course 3 by ELISA.
|
|---|---|
|
Overall Study
STARTED
|
27
|
|
Overall Study
COMPLETED
|
27
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Bevacizumab and Erlotinib in Treating Patients With Advanced Liver Cancer
Baseline characteristics by cohort
| Measure |
Treatment (Bevacizumab and Erlotinib)
n=27 Participants
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory studies to determine EGFR and phosphorylated-EGFR protein levels using initial diagnostic biopsy specimens by IHC for correlation with clinical outcome. Levels of proteins through which EGFR signals, including Akt, phosphorylated-Akt, MAPK, and phosphorylated-MAPK, are also determined using initial diagnostic biopsy specimens by IHC and correlated with clinical outcome. Total and free serum vascular endothelial growth factor levels are determined at the start of study and prior to course 3 by ELISA.
|
|---|---|
|
Age, Continuous
All Patients
|
60 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
27 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Patients were able to continue treatment indefinitely and were evaluated every cycle until discontinued treatment.Population: Four patients were inevaluable because they were off the study prior to first radiologic evaluation for objective response.
Responses to erlotinib and bevacizumab treatment were evaluated using Response Evaluation Criteria In Solid Tumors (RECIST). A Complete Response (CR) is defined as the disappearance of all target lesions. A Partial Response (PR) is defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum of the longest diameters.
Outcome measures
| Measure |
Treatment (Bevacizumab and Erlotinib)
n=23 Participants
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory studies to determine EGFR and phosphorylated-EGFR protein levels using initial diagnostic biopsy specimens by IHC for correlation with clinical outcome. Levels of proteins through which EGFR signals, including Akt, phosphorylated-Akt, MAPK, and phosphorylated-MAPK, are also determined using initial diagnostic biopsy specimens by IHC and correlated with clinical outcome. Total and free serum vascular endothelial growth factor levels are determined at the start of study and prior to course 3 by ELISA.
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|---|---|
|
Number of Patients With Confirmed Tumor Response Defined to be Either a Complete Response (CR) or Partial Response (PR).
Complete Response (CR)
|
0 participants
|
|
Number of Patients With Confirmed Tumor Response Defined to be Either a Complete Response (CR) or Partial Response (PR).
Partial Response (PR)
|
1 participants
|
SECONDARY outcome
Timeframe: From registration to death due to any cause, patients are followed up to 3 years after treatmentPopulation: All 27 patients were analyzed.
Survival time is defined as the time from registration to death due to any cause. Estimated using the method of Kaplan-Meier.
Outcome measures
| Measure |
Treatment (Bevacizumab and Erlotinib)
n=27 Participants
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory studies to determine EGFR and phosphorylated-EGFR protein levels using initial diagnostic biopsy specimens by IHC for correlation with clinical outcome. Levels of proteins through which EGFR signals, including Akt, phosphorylated-Akt, MAPK, and phosphorylated-MAPK, are also determined using initial diagnostic biopsy specimens by IHC and correlated with clinical outcome. Total and free serum vascular endothelial growth factor levels are determined at the start of study and prior to course 3 by ELISA.
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|---|---|
|
Survival Time
|
9.5 months
Interval 7.1 to 17.1
|
SECONDARY outcome
Timeframe: From registration to documentation of disease progression, up to 3 years after treatment.Population: All 27 patients were included in the analysis.
Time to disease progression is defined as the time from registration to documentation of disease progression. Estimated using the method of Kaplan-Meier.
Outcome measures
| Measure |
Treatment (Bevacizumab and Erlotinib)
n=27 Participants
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory studies to determine EGFR and phosphorylated-EGFR protein levels using initial diagnostic biopsy specimens by IHC for correlation with clinical outcome. Levels of proteins through which EGFR signals, including Akt, phosphorylated-Akt, MAPK, and phosphorylated-MAPK, are also determined using initial diagnostic biopsy specimens by IHC and correlated with clinical outcome. Total and free serum vascular endothelial growth factor levels are determined at the start of study and prior to course 3 by ELISA.
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|---|---|
|
Time to Disease Progression
|
3.0 months
Interval 1.8 to 7.1
|
SECONDARY outcome
Timeframe: The date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented.Population: No patients were analyzed for this secondary outcome due to insufficient data.
Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From the date of randomization to the date at which the patient is removed from treatment due to progression, toxicity, or refusal.Population: All 27 patients were used in this analysis.
Time to treatment failure is defined to be the time from the date of randomization to the date at which the patient is removed from treatment due to progression, toxicity, or refusal.
Outcome measures
| Measure |
Treatment (Bevacizumab and Erlotinib)
n=27 Participants
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory studies to determine EGFR and phosphorylated-EGFR protein levels using initial diagnostic biopsy specimens by IHC for correlation with clinical outcome. Levels of proteins through which EGFR signals, including Akt, phosphorylated-Akt, MAPK, and phosphorylated-MAPK, are also determined using initial diagnostic biopsy specimens by IHC and correlated with clinical outcome. Total and free serum vascular endothelial growth factor levels are determined at the start of study and prior to course 3 by ELISA.
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|---|---|
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Time to Treatment Failure
|
2.0 months
Interval 1.8 to 4.6
|
Adverse Events
Treatment (Bevacizumab and Erlotinib)
Serious events: 14 serious events
Other events: 26 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treatment (Bevacizumab and Erlotinib)
n=27 participants at risk
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory studies to determine EGFR and phosphorylated-EGFR protein levels using initial diagnostic biopsy specimens by IHC for correlation with clinical outcome. Levels of proteins through which EGFR signals, including Akt, phosphorylated-Akt, MAPK, and phosphorylated-MAPK, are also determined using initial diagnostic biopsy specimens by IHC and correlated with clinical outcome. Total and free serum vascular endothelial growth factor levels are determined at the start of study and prior to course 3 by ELISA.
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|---|---|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
3.7%
1/27 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
7.4%
2/27 • Number of events 2
|
|
Gastrointestinal disorders
Diarrhea
|
11.1%
3/27 • Number of events 3
|
|
Gastrointestinal disorders
Upper gastrointestinal hemorrhage
|
3.7%
1/27 • Number of events 1
|
|
General disorders
Fatigue
|
3.7%
1/27 • Number of events 1
|
|
General disorders
Fever
|
7.4%
2/27 • Number of events 2
|
|
Infections and infestations
Infection
|
3.7%
1/27 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
3.7%
1/27 • Number of events 1
|
|
Investigations
Aspartate aminotransferase increased
|
3.7%
1/27 • Number of events 1
|
|
Investigations
Bilirubin increased
|
3.7%
1/27 • Number of events 1
|
|
Investigations
Creatinine increased
|
3.7%
1/27 • Number of events 1
|
|
Metabolism and nutrition disorders
Dehydration
|
3.7%
1/27 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
3.7%
1/27 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
3.7%
1/27 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypokalemia
|
3.7%
1/27 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyponatremia
|
3.7%
1/27 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
Encephalopathy
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
Neurological disorder NOS
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
3.7%
1/27 • Number of events 1
|
|
Renal and urinary disorders
Kidney pain
|
3.7%
1/27 • Number of events 1
|
|
Renal and urinary disorders
Renal hemorrhage
|
3.7%
1/27 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
3.7%
1/27 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
3.7%
1/27 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory disorder
|
3.7%
1/27 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Hand-and-foot syndrome
|
3.7%
1/27 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash desquamating
|
7.4%
2/27 • Number of events 2
|
|
Vascular disorders
Hypotension
|
3.7%
1/27 • Number of events 1
|
Other adverse events
| Measure |
Treatment (Bevacizumab and Erlotinib)
n=27 participants at risk
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory studies to determine EGFR and phosphorylated-EGFR protein levels using initial diagnostic biopsy specimens by IHC for correlation with clinical outcome. Levels of proteins through which EGFR signals, including Akt, phosphorylated-Akt, MAPK, and phosphorylated-MAPK, are also determined using initial diagnostic biopsy specimens by IHC and correlated with clinical outcome. Total and free serum vascular endothelial growth factor levels are determined at the start of study and prior to course 3 by ELISA.
|
|---|---|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
14.8%
4/27 • Number of events 6
|
|
Eye disorders
Eye disorder
|
3.7%
1/27 • Number of events 2
|
|
Eye disorders
Keratitis
|
7.4%
2/27 • Number of events 3
|
|
Gastrointestinal disorders
Abdominal pain
|
7.4%
2/27 • Number of events 2
|
|
Gastrointestinal disorders
Diarrhea
|
63.0%
17/27 • Number of events 44
|
|
Gastrointestinal disorders
Ear, nose and throat examination abnormal
|
7.4%
2/27 • Number of events 2
|
|
Gastrointestinal disorders
Hemorrhoids
|
3.7%
1/27 • Number of events 2
|
|
Gastrointestinal disorders
Mucositis oral
|
14.8%
4/27 • Number of events 6
|
|
Gastrointestinal disorders
Nausea
|
11.1%
3/27 • Number of events 7
|
|
Gastrointestinal disorders
Oral hemorrhage
|
3.7%
1/27 • Number of events 1
|
|
Gastrointestinal disorders
Oral pain
|
3.7%
1/27 • Number of events 1
|
|
Gastrointestinal disorders
Rectal fistula
|
3.7%
1/27 • Number of events 1
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
3.7%
1/27 • Number of events 1
|
|
Gastrointestinal disorders
Upper gastrointestinal hemorrhage
|
3.7%
1/27 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
7.4%
2/27 • Number of events 2
|
|
General disorders
Fatigue
|
48.1%
13/27 • Number of events 24
|
|
Infections and infestations
Wound infection
|
3.7%
1/27 • Number of events 1
|
|
Investigations
Alanine aminotransferase increased
|
18.5%
5/27 • Number of events 12
|
|
Investigations
Alkaline phosphatase increased
|
3.7%
1/27 • Number of events 2
|
|
Investigations
Aspartate aminotransferase increased
|
14.8%
4/27 • Number of events 10
|
|
Investigations
Creatinine increased
|
7.4%
2/27 • Number of events 2
|
|
Investigations
INR increased
|
3.7%
1/27 • Number of events 2
|
|
Investigations
Leukocyte count decreased
|
3.7%
1/27 • Number of events 2
|
|
Investigations
Platelet count decreased
|
7.4%
2/27 • Number of events 7
|
|
Investigations
Weight loss
|
11.1%
3/27 • Number of events 4
|
|
Metabolism and nutrition disorders
Anorexia
|
18.5%
5/27 • Number of events 5
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
3.7%
1/27 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
18.5%
5/27 • Number of events 7
|
|
Metabolism and nutrition disorders
Hyponatremia
|
7.4%
2/27 • Number of events 2
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
3.7%
1/27 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.7%
1/27 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Joint pain
|
7.4%
2/27 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
3.7%
1/27 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
Depressed level of consciousness
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
11.1%
3/27 • Number of events 3
|
|
Nervous system disorders
Headache
|
7.4%
2/27 • Number of events 3
|
|
Nervous system disorders
Neurological disorder NOS
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
Tremor
|
3.7%
1/27 • Number of events 1
|
|
Psychiatric disorders
Confusion
|
3.7%
1/27 • Number of events 2
|
|
Renal and urinary disorders
Proteinuria
|
3.7%
1/27 • Number of events 3
|
|
Renal and urinary disorders
Urinary frequency
|
3.7%
1/27 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
25.9%
7/27 • Number of events 13
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
25.9%
7/27 • Number of events 9
|
|
Respiratory, thoracic and mediastinal disorders
Hemorrhage nasal
|
7.4%
2/27 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
3.7%
1/27 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Voice alteration
|
3.7%
1/27 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
3.7%
1/27 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
3.7%
1/27 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
14.8%
4/27 • Number of events 10
|
|
Skin and subcutaneous tissue disorders
Rash desquamating
|
70.4%
19/27 • Number of events 63
|
|
Skin and subcutaneous tissue disorders
Skin disorder
|
3.7%
1/27 • Number of events 1
|
|
Vascular disorders
Hypertension
|
40.7%
11/27 • Number of events 17
|
|
Vascular disorders
Hypotension
|
3.7%
1/27 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60