Trial Outcomes & Findings for A Study of Tarceva (Erlotinib) and Avastin (Bevacizumab) in Patients With Advanced or Metastatic Liver Cancer. (NCT NCT00605722)
NCT ID: NCT00605722
Last Updated: 2014-07-14
Results Overview
Percentage of participants who were alive and without documented progressive disease 16 weeks after their first dose of study drug. Diagnosis of Progressive Disease was made by objective criteria (RECIST criteria) on the target lesion(s), or by documenting, with Computerised Tomography/Magnetic Resonance Imaging (CT/MRI) scans, the presence of newly occurring lesion(s) arising outside the scanned areas of the target lesions. PD required at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
COMPLETED
PHASE2
51 participants
Week 16
2014-07-14
Participant Flow
Participant milestones
| Measure |
Bevacizumab + Erlotinib
Participants received bevacizumab (Avastin) 5 mg/kg intravenous (iv) on day 1 of each 2 week cycle plus erlotinib (Tarceva) 150 mg orally once a day until disease progression or unmanageable toxicity.
|
|---|---|
|
Overall Study
STARTED
|
51
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
51
|
Reasons for withdrawal
| Measure |
Bevacizumab + Erlotinib
Participants received bevacizumab (Avastin) 5 mg/kg intravenous (iv) on day 1 of each 2 week cycle plus erlotinib (Tarceva) 150 mg orally once a day until disease progression or unmanageable toxicity.
|
|---|---|
|
Overall Study
Adverse Event
|
6
|
|
Overall Study
Insufficient therapeutic response
|
44
|
|
Overall Study
Failure to return
|
1
|
Baseline Characteristics
A Study of Tarceva (Erlotinib) and Avastin (Bevacizumab) in Patients With Advanced or Metastatic Liver Cancer.
Baseline characteristics by cohort
| Measure |
Bevacizumab + Erlotinib
n=51 Participants
Participants received bevacizumab (Avastin) 5 mg/kg intravenous (iv) on day 1 of each 2 week cycle plus erlotinib (Tarceva) 150 mg orally once a day until disease progression or unmanageable toxicity.
|
|---|---|
|
Age, Continuous
|
53.9 years
STANDARD_DEVIATION 14.80 • n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
44 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 16Population: Intent-to-treat population included all participants who received study drug. Participants who had neither progressed nor died at the time of study completion or who were lost to follow-up were censored at the date of the last tumor assessment or last follow up for progression of disease.
Percentage of participants who were alive and without documented progressive disease 16 weeks after their first dose of study drug. Diagnosis of Progressive Disease was made by objective criteria (RECIST criteria) on the target lesion(s), or by documenting, with Computerised Tomography/Magnetic Resonance Imaging (CT/MRI) scans, the presence of newly occurring lesion(s) arising outside the scanned areas of the target lesions. PD required at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Outcome measures
| Measure |
Bevacizumab + Erlotinib
n=51 Participants
Participants received bevacizumab (Avastin) 5 mg/kg intravenous (iv) on day 1 of each 2 week cycle plus erlotinib (Tarceva) 150 mg orally once a day until disease progression or unmanageable toxicity.
|
|---|---|
|
Percentage of Participants With Progression-free Survival (PFS)
|
35.3 percentage of participants
Interval 22.4 to 49.9
|
SECONDARY outcome
Timeframe: Event driven (median follow-up 12 months)Population: Intent-to-treat population included all participants who received study drug.
ORR was defined as the percentage of participants with Complete Response (CR) or Partial Response (PR). Analysis of tumor response was based on the best overall response according to Response Evaluation Criteria in Solid Tumors (RECIST), which was defined as the best response recorded from the start of trial treatment until disease progression/recurrence (or death), taking as reference for progressive disease (PD) the smallest measurements recorded since the treatment started. CR was defined as the disappearance of all target lesions; for non-target lesions disappearance of lesions and normal tumour marker levels. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, using as reference the Baseline sum LD. PD required at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Outcome measures
| Measure |
Bevacizumab + Erlotinib
n=51 Participants
Participants received bevacizumab (Avastin) 5 mg/kg intravenous (iv) on day 1 of each 2 week cycle plus erlotinib (Tarceva) 150 mg orally once a day until disease progression or unmanageable toxicity.
|
|---|---|
|
Overall Response Rate (ORR)
Complete Response
|
0.0 percentage of participants
Interval 0.0 to 7.0
|
|
Overall Response Rate (ORR)
Partial Response
|
5.9 percentage of participants
Interval 1.2 to 16.2
|
SECONDARY outcome
Timeframe: Event driven (median follow-up 12 months)Population: Intent-to-treat population included all participants who received study drug.
Disease Control Rate was defined as the percentage of participants with Complete Response (CR), Partial Response (PR) or Stable Disease (SD) for at least 8 weeks by Response Evaluation Criteria in Solid Tumours (RECIST). CR was defined as the disappearance of all target lesions; for non-target lesions disappearance of lesions and normal tumour marker levels. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, using as reference the Baseline sum LD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started; for non-target lesions persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits.
Outcome measures
| Measure |
Bevacizumab + Erlotinib
n=51 Participants
Participants received bevacizumab (Avastin) 5 mg/kg intravenous (iv) on day 1 of each 2 week cycle plus erlotinib (Tarceva) 150 mg orally once a day until disease progression or unmanageable toxicity.
|
|---|---|
|
Disease Control Rate (DCR)
|
52.9 Percentage of participants
Interval 38.5 to 67.1
|
SECONDARY outcome
Timeframe: Event driven (median follow-up 12 months)Population: Intent-to-treat population included all participants who received study drug.
Time to tumor progression was defined as the time period in months from the start of study drug treatment to disease progression. Progressive disease required at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Outcome measures
| Measure |
Bevacizumab + Erlotinib
n=51 Participants
Participants received bevacizumab (Avastin) 5 mg/kg intravenous (iv) on day 1 of each 2 week cycle plus erlotinib (Tarceva) 150 mg orally once a day until disease progression or unmanageable toxicity.
|
|---|---|
|
Time to Tumor Progression
|
2.9 Months
Interval 1.8 to 5.3
|
SECONDARY outcome
Timeframe: Event driven (median follow-up 12 months)Population: Intent-to-treat population included all participants who received study drug. Participants were censored at the last follow-up visit.
PFS was defined as the time period in months from the start of study drug treatment to the first of either progression or death. Progressive disease required at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Outcome measures
| Measure |
Bevacizumab + Erlotinib
n=51 Participants
Participants received bevacizumab (Avastin) 5 mg/kg intravenous (iv) on day 1 of each 2 week cycle plus erlotinib (Tarceva) 150 mg orally once a day until disease progression or unmanageable toxicity.
|
|---|---|
|
Progression-free Survival (PFS)
|
2.9 months
Interval 1.8 to 4.8
|
SECONDARY outcome
Timeframe: Event driven (median follow-up 12 months)Population: Intent-to-treat population included all participants who received study drug.
OS was defined as the time period in months from the start of study drug treatment to death.
Outcome measures
| Measure |
Bevacizumab + Erlotinib
n=51 Participants
Participants received bevacizumab (Avastin) 5 mg/kg intravenous (iv) on day 1 of each 2 week cycle plus erlotinib (Tarceva) 150 mg orally once a day until disease progression or unmanageable toxicity.
|
|---|---|
|
Overall Survival (OS)
|
10.7 months
Interval 7.4 to
Kaplan-Meier estimate; Confidence Interval (CI) was not estimated due to the small number of participants with events.
|
SECONDARY outcome
Timeframe: Up to 107 WeeksPopulation: Safety population included all participants who received at least one dose of study drug.
An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. A SAE was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Outcome measures
| Measure |
Bevacizumab + Erlotinib
n=51 Participants
Participants received bevacizumab (Avastin) 5 mg/kg intravenous (iv) on day 1 of each 2 week cycle plus erlotinib (Tarceva) 150 mg orally once a day until disease progression or unmanageable toxicity.
|
|---|---|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Serious Adverse Events
|
19 participants
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Adverse Events
|
51 participants
|
Adverse Events
Bevacizumab + Erlotinib
Serious adverse events
| Measure |
Bevacizumab + Erlotinib
n=51 participants at risk
Participants received bevacizumab (Avastin) 5 mg/kg intravenous (iv) on day 1 of each 2 week cycle plus erlotinib (Tarceva) 150 mg orally once a day until disease progression or unmanageable toxicity.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
5.9%
3/51 • Up to 107 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
3.9%
2/51 • Up to 107 weeks
|
|
Gastrointestinal disorders
Upper gastrointestinal hemorrhage
|
3.9%
2/51 • Up to 107 weeks
|
|
General disorders
Tumor associated fever
|
3.9%
2/51 • Up to 107 weeks
|
|
Gastrointestinal disorders
Duodenal ulcer hemorrhage
|
2.0%
1/51 • Up to 107 weeks
|
|
Gastrointestinal disorders
Gastric ulcer
|
2.0%
1/51 • Up to 107 weeks
|
|
Gastrointestinal disorders
Gastric varices hemorrhage
|
2.0%
1/51 • Up to 107 weeks
|
|
Gastrointestinal disorders
Melena
|
2.0%
1/51 • Up to 107 weeks
|
|
Gastrointestinal disorders
Peptic ulcer
|
2.0%
1/51 • Up to 107 weeks
|
|
Blood and lymphatic system disorders
Neutropenia
|
2.0%
1/51 • Up to 107 weeks
|
|
Infections and infestations
Anal abscess
|
2.0%
1/51 • Up to 107 weeks
|
|
Blood and lymphatic system disorders
Bacteremia
|
2.0%
1/51 • Up to 107 weeks
|
|
Infections and infestations
Enterobacter infection
|
2.0%
1/51 • Up to 107 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
2.0%
1/51 • Up to 107 weeks
|
|
Renal and urinary disorders
Hepatic failure
|
2.0%
1/51 • Up to 107 weeks
|
|
Hepatobiliary disorders
Hyperbilirubinemia
|
2.0%
1/51 • Up to 107 weeks
|
|
Hepatobiliary disorders
Jaundice cholestatic
|
2.0%
1/51 • Up to 107 weeks
|
|
General disorders
Tumor pain
|
2.0%
1/51 • Up to 107 weeks
|
|
Endocrine disorders
Inappropriate anti-diuretic hormone secretion
|
2.0%
1/51 • Up to 107 weeks
|
|
General disorders
Pyrexia
|
2.0%
1/51 • Up to 107 weeks
|
|
Investigations
Transaminase increased
|
2.0%
1/51 • Up to 107 weeks
|
|
Metabolism and nutrition disorders
Decreased appetite
|
2.0%
1/51 • Up to 107 weeks
|
|
Hepatobiliary disorders
Hepatic encephalopathy
|
2.0%
1/51 • Up to 107 weeks
|
|
Blood and lymphatic system disorders
Bleeding varicose vein
|
2.0%
1/51 • Up to 107 weeks
|
Other adverse events
| Measure |
Bevacizumab + Erlotinib
n=51 participants at risk
Participants received bevacizumab (Avastin) 5 mg/kg intravenous (iv) on day 1 of each 2 week cycle plus erlotinib (Tarceva) 150 mg orally once a day until disease progression or unmanageable toxicity.
|
|---|---|
|
Skin and subcutaneous tissue disorders
Rash
|
70.6%
36/51 • Up to 107 weeks
|
|
Skin and subcutaneous tissue disorders
Acne
|
43.1%
22/51 • Up to 107 weeks
|
|
Skin and subcutaneous tissue disorders
Palmer-Plantar erythrodysaesthesis syndrome
|
21.6%
11/51 • Up to 107 weeks
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
21.6%
11/51 • Up to 107 weeks
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
13.7%
7/51 • Up to 107 weeks
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
11.8%
6/51 • Up to 107 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
51.0%
26/51 • Up to 107 weeks
|
|
Gastrointestinal disorders
Nausea
|
23.5%
12/51 • Up to 107 weeks
|
|
Gastrointestinal disorders
Vomiting
|
21.6%
11/51 • Up to 107 weeks
|
|
Gastrointestinal disorders
Constipation
|
15.7%
8/51 • Up to 107 weeks
|
|
Gastrointestinal disorders
Stomatitis
|
13.7%
7/51 • Up to 107 weeks
|
|
Gastrointestinal disorders
Abdominal pain upper
|
11.8%
6/51 • Up to 107 weeks
|
|
Gastrointestinal disorders
Gastric ulcer
|
11.8%
6/51 • Up to 107 weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
9.8%
5/51 • Up to 107 weeks
|
|
Gastrointestinal disorders
Abdominal distension
|
7.8%
4/51 • Up to 107 weeks
|
|
Gastrointestinal disorders
Gingival bleeding
|
5.9%
3/51 • Up to 107 weeks
|
|
Gastrointestinal disorders
Melena
|
5.9%
3/51 • Up to 107 weeks
|
|
Gastrointestinal disorders
Mouth ulceration
|
5.9%
3/51 • Up to 107 weeks
|
|
Gastrointestinal disorders
Varices esophageal
|
5.9%
3/51 • Up to 107 weeks
|
|
General disorders
Pyrexia
|
25.5%
13/51 • Up to 107 weeks
|
|
General disorders
Fatigue
|
17.6%
9/51 • Up to 107 weeks
|
|
General disorders
Edema peripheral
|
9.8%
5/51 • Up to 107 weeks
|
|
General disorders
Asthenia
|
7.8%
4/51 • Up to 107 weeks
|
|
General disorders
Chest pain
|
5.9%
3/51 • Up to 107 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
19.6%
10/51 • Up to 107 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
13.7%
7/51 • Up to 107 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.8%
6/51 • Up to 107 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Hemoptysis
|
9.8%
5/51 • Up to 107 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
9.8%
5/51 • Up to 107 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
7.8%
4/51 • Up to 107 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
5.9%
3/51 • Up to 107 weeks
|
|
Infections and infestations
Paronychia
|
19.6%
10/51 • Up to 107 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
5.9%
3/51 • Up to 107 weeks
|
|
Infections and infestations
Urinary tract infection
|
5.9%
3/51 • Up to 107 weeks
|
|
Metabolism and nutrition disorders
Decreased appetite
|
39.2%
20/51 • Up to 107 weeks
|
|
Investigations
Weight decreased
|
17.6%
9/51 • Up to 107 weeks
|
|
Investigations
Alanine aminotransferase increased
|
7.8%
4/51 • Up to 107 weeks
|
|
Investigations
Aspartate aminotransferase increased
|
7.8%
4/51 • Up to 107 weeks
|
|
Nervous system disorders
Dizziness
|
13.7%
7/51 • Up to 107 weeks
|
|
Nervous system disorders
Dysgeusia
|
5.9%
3/51 • Up to 107 weeks
|
|
Renal and urinary disorders
Proteinuria
|
11.8%
6/51 • Up to 107 weeks
|
|
Renal and urinary disorders
Hematuria
|
5.9%
3/51 • Up to 107 weeks
|
|
Psychiatric disorders
Insomnia
|
15.7%
8/51 • Up to 107 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.9%
3/51 • Up to 107 weeks
|
|
Blood and lymphatic system disorders
Anemia
|
11.8%
6/51 • Up to 107 weeks
|
|
Vascular disorders
Hypertension
|
11.8%
6/51 • Up to 107 weeks
|
|
Hepatobiliary disorders
Hyperbilirubinemia
|
9.8%
5/51 • Up to 107 weeks
|
|
Eye disorders
Cataract
|
5.9%
3/51 • Up to 107 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER