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A Study of Tarceva (Erlotinib) and Avastin (Bevacizumab) in Patients With Advanced or Metastatic Liver Cancer.

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ClinicalTrials.gov Identifier: NCT00605722
Recruitment Status : Completed
First Posted : January 31, 2008
Results First Posted : July 14, 2014
Last Update Posted : July 14, 2014
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Liver Cancer
Interventions Drug: bevacizumab (Avastin)
Drug: erlotinib (Tarceva)
Enrollment 51
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Bevacizumab + Erlotinib
Hide Arm/Group Description 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.
Period Title: Overall Study
Started 51
Completed 0 [1]
Not Completed 51
Reason Not Completed
Adverse Event             6
Insufficient therapeutic response             44
Failure to return             1
[1]
Completed=Completed Treatment.
Arm/Group Title Bevacizumab + Erlotinib
Hide Arm/Group Description 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 Number of Baseline Participants 51
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 51 participants
53.9  (14.80)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants
Female
7
  13.7%
Male
44
  86.3%
1.Primary Outcome
Title Percentage of Participants With Progression-free Survival (PFS)
Hide Description 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.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Bevacizumab + Erlotinib
Hide Arm/Group Description:
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 Number of Participants Analyzed 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
35.3
(22.4 to 49.9)
2.Secondary Outcome
Title Overall Response Rate (ORR)
Hide Description 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.
Time Frame Event driven (median follow-up 12 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population included all participants who received study drug.
Arm/Group Title Bevacizumab + Erlotinib
Hide Arm/Group Description:
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 Number of Participants Analyzed 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Complete Response
0.0
(0.0 to 7.0)
Partial Response
5.9
(1.2 to 16.2)
3.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description 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.
Time Frame Event driven (median follow-up 12 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population included all participants who received study drug.
Arm/Group Title Bevacizumab + Erlotinib
Hide Arm/Group Description:
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 Number of Participants Analyzed 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
52.9
(38.5 to 67.1)
4.Secondary Outcome
Title Time to Tumor Progression
Hide Description 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.
Time Frame Event driven (median follow-up 12 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population included all participants who received study drug.
Arm/Group Title Bevacizumab + Erlotinib
Hide Arm/Group Description:
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 Number of Participants Analyzed 51
Median (95% Confidence Interval)
Unit of Measure: Months
2.9
(1.8 to 5.3)
5.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description 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.
Time Frame Event driven (median follow-up 12 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population included all participants who received study drug. Participants were censored at the last follow-up visit.
Arm/Group Title Bevacizumab + Erlotinib
Hide Arm/Group Description:
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 Number of Participants Analyzed 51
Median (95% Confidence Interval)
Unit of Measure: months
2.9
(1.8 to 4.8)
6.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time period in months from the start of study drug treatment to death.
Time Frame Event driven (median follow-up 12 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population included all participants who received study drug.
Arm/Group Title Bevacizumab + Erlotinib
Hide Arm/Group Description:
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 Number of Participants Analyzed 51
Median (95% Confidence Interval)
Unit of Measure: months
10.7 [1] 
(7.4 to NA)
[1]
Kaplan-Meier estimate; Confidence Interval (CI) was not estimated due to the small number of participants with events.
7.Secondary Outcome
Title Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description 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.
Time Frame Up to 107 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received at least one dose of study drug.
Arm/Group Title Bevacizumab + Erlotinib
Hide Arm/Group Description:
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 Number of Participants Analyzed 51
Measure Type: Number
Unit of Measure: participants
Serious Adverse Events 19
Adverse Events 51
Time Frame Up to 107 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Bevacizumab + Erlotinib
Hide Arm/Group Description 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.
All-Cause Mortality
Bevacizumab + Erlotinib
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Bevacizumab + Erlotinib
Affected / at Risk (%)
Total   19/51 (37.25%) 
Blood and lymphatic system disorders   
Anemia  1  3/51 (5.88%) 
Neutropenia  1  1/51 (1.96%) 
Bacteremia  1  1/51 (1.96%) 
Bleeding varicose vein  1  1/51 (1.96%) 
Endocrine disorders   
Inappropriate anti-diuretic hormone secretion  1  1/51 (1.96%) 
Gastrointestinal disorders   
Diarrhea  1  2/51 (3.92%) 
Upper gastrointestinal hemorrhage  1  2/51 (3.92%) 
Duodenal ulcer hemorrhage  1  1/51 (1.96%) 
Gastric ulcer  1  1/51 (1.96%) 
Gastric varices hemorrhage  1  1/51 (1.96%) 
Melena  1  1/51 (1.96%) 
Peptic ulcer  1  1/51 (1.96%) 
General disorders   
Tumor associated fever  1  2/51 (3.92%) 
Tumor pain  1  1/51 (1.96%) 
Pyrexia  1  1/51 (1.96%) 
Hepatobiliary disorders   
Hyperbilirubinemia  1  1/51 (1.96%) 
Jaundice cholestatic  1  1/51 (1.96%) 
Hepatic encephalopathy  1  1/51 (1.96%) 
Infections and infestations   
Anal abscess  1  1/51 (1.96%) 
Enterobacter infection  1  1/51 (1.96%) 
Investigations   
Transaminase increased  1  1/51 (1.96%) 
Metabolism and nutrition disorders   
Decreased appetite  1  1/51 (1.96%) 
Renal and urinary disorders   
Hepatic failure  1  1/51 (1.96%) 
Respiratory, thoracic and mediastinal disorders   
Pneumonia  1  1/51 (1.96%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bevacizumab + Erlotinib
Affected / at Risk (%)
Total   51/51 (100.00%) 
Blood and lymphatic system disorders   
Anemia  1  6/51 (11.76%) 
Eye disorders   
Cataract  1  3/51 (5.88%) 
Gastrointestinal disorders   
Diarrhea  1  26/51 (50.98%) 
Nausea  1  12/51 (23.53%) 
Vomiting  1  11/51 (21.57%) 
Constipation  1  8/51 (15.69%) 
Stomatitis  1  7/51 (13.73%) 
Abdominal pain upper  1  6/51 (11.76%) 
Gastric ulcer  1  6/51 (11.76%) 
Abdominal pain  1  5/51 (9.80%) 
Abdominal distension  1  4/51 (7.84%) 
Gingival bleeding  1  3/51 (5.88%) 
Melena  1  3/51 (5.88%) 
Mouth ulceration  1  3/51 (5.88%) 
Varices esophageal  1  3/51 (5.88%) 
General disorders   
Pyrexia  1  13/51 (25.49%) 
Fatigue  1  9/51 (17.65%) 
Edema peripheral  1  5/51 (9.80%) 
Asthenia  1  4/51 (7.84%) 
Chest pain  1  3/51 (5.88%) 
Hepatobiliary disorders   
Hyperbilirubinemia  1  5/51 (9.80%) 
Infections and infestations   
Paronychia  1  10/51 (19.61%) 
Upper respiratory tract infection  1  3/51 (5.88%) 
Urinary tract infection  1  3/51 (5.88%) 
Investigations   
Weight decreased  1  9/51 (17.65%) 
Alanine aminotransferase increased  1  4/51 (7.84%) 
Aspartate aminotransferase increased  1  4/51 (7.84%) 
Metabolism and nutrition disorders   
Decreased appetite  1  20/51 (39.22%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  3/51 (5.88%) 
Nervous system disorders   
Dizziness  1  7/51 (13.73%) 
Dysgeusia  1  3/51 (5.88%) 
Psychiatric disorders   
Insomnia  1  8/51 (15.69%) 
Renal and urinary disorders   
Proteinuria  1  6/51 (11.76%) 
Hematuria  1  3/51 (5.88%) 
Respiratory, thoracic and mediastinal disorders   
Epistaxis  1  10/51 (19.61%) 
Dyspnoea  1  7/51 (13.73%) 
Cough  1  6/51 (11.76%) 
Hemoptysis  1  5/51 (9.80%) 
Hiccups  1  5/51 (9.80%) 
Oropharyngeal pain  1  4/51 (7.84%) 
Dysphonia  1  3/51 (5.88%) 
Skin and subcutaneous tissue disorders   
Rash  1  36/51 (70.59%) 
Acne  1  22/51 (43.14%) 
Palmer-Plantar erythrodysaesthesis syndrome  1  11/51 (21.57%) 
Pruritus  1  11/51 (21.57%) 
Alopecia  1  7/51 (13.73%) 
Dry skin  1  6/51 (11.76%) 
Vascular disorders   
Hypertension  1  6/51 (11.76%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffman-LaRoche
Phone: 800-821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00605722     History of Changes
Other Study ID Numbers: ML21213
First Submitted: January 18, 2008
First Posted: January 31, 2008
Results First Submitted: June 12, 2014
Results First Posted: July 14, 2014
Last Update Posted: July 14, 2014