Trial Outcomes & Findings for Bevacizumab and Erlotinib Hydrochloride in Treating Patients With Metastatic or Unresectable Biliary Tumors (NCT NCT00356889)
NCT ID: NCT00356889
Last Updated: 2014-05-28
Results Overview
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the target lesions. A confirmed tumor response is defined to be either a Complete Response or a Partial Response noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. Confirmed tumor responses will be evaluated using the first 6 cycles of treatment. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment and had one post-baseline disease assessment will be evaluable for response. Forty-nine of the 53 eligible patients had at least one post-baseline disease assessment and were evaluable for this endpoint.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
56 participants
Primary outcome timeframe
After 6 courses of treatment. Each course lasts 28 days.
Results posted on
2014-05-28
Participant Flow
Fifty-six patients were enrolled between August 2006 and April 2008 at eight sites in the Phase II Consortium. The data are reported as of November 2009.
Three patients were ineligible after starting treatment (brain metastases, alteration in diagnosis, colitis). Two of these participants reported adverse events. Therefore, 56 participants were used for baseline, 53 patients were used for endpoint analyses, and 55 participants were used to report toxicity.
Participant milestones
| Measure |
Bevacizumab and Erlotinib Hydrochloride
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.
Tumor tissue and blood specimens are collected periodically for correlative studies. Specimens are examined by immunohistochemistry for epidermal growth factor receptor (EGFR) and P-EGFR protein levels; AKT p-AKT, mitogen-activated protein kinase (MAPK) and P-MAPK protein levels; and vascular endothelial growth factor receptor (VEGFR)-1 and VEGFR-2 protein levels. EGFR mutations are detected by laser capture microdissection. Enzyme-linked immunosorbent assay is used to measure total and free serum VEGF levels.
|
|---|---|
|
Overall Study
STARTED
|
56
|
|
Overall Study
COMPLETED
|
53
|
|
Overall Study
NOT COMPLETED
|
3
|
Reasons for withdrawal
| Measure |
Bevacizumab and Erlotinib Hydrochloride
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.
Tumor tissue and blood specimens are collected periodically for correlative studies. Specimens are examined by immunohistochemistry for epidermal growth factor receptor (EGFR) and P-EGFR protein levels; AKT p-AKT, mitogen-activated protein kinase (MAPK) and P-MAPK protein levels; and vascular endothelial growth factor receptor (VEGFR)-1 and VEGFR-2 protein levels. EGFR mutations are detected by laser capture microdissection. Enzyme-linked immunosorbent assay is used to measure total and free serum VEGF levels.
|
|---|---|
|
Overall Study
Protocol Violation
|
2
|
|
Overall Study
Adverse Event
|
1
|
Baseline Characteristics
Bevacizumab and Erlotinib Hydrochloride in Treating Patients With Metastatic or Unresectable Biliary Tumors
Baseline characteristics by cohort
| Measure |
Bevacizumab and Erlotinib Hydrochloride
n=56 Participants
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Tumor tissue and blood specimens are collected periodically for correlative studies. Specimens are examined by immunohistochemistry for epidermal growth factor receptor (EGFR) and P-EGFR protein levels; AKT p-AKT, mitogen-activated protein kinase (MAPK) and P-MAPK protein levels; and vascular endothelial growth factor receptor (VEGFR)-1 and VEGFR-2 protein levels. EGFR mutations are detected by laser capture microdissection. Enzyme-linked immunosorbent assay is used to measure total and free serum VEGF levels.
|
|---|---|
|
Age, Continuous
|
63.5 years
n=93 Participants
|
|
Sex: Female, Male
Female
|
32 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
50 participants
n=93 Participants
|
|
Region of Enrollment
Australia
|
2 participants
n=93 Participants
|
|
Region of Enrollment
Singapore
|
4 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: After 6 courses of treatment. Each course lasts 28 days.Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the target lesions. A confirmed tumor response is defined to be either a Complete Response or a Partial Response noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. Confirmed tumor responses will be evaluated using the first 6 cycles of treatment. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment and had one post-baseline disease assessment will be evaluable for response. Forty-nine of the 53 eligible patients had at least one post-baseline disease assessment and were evaluable for this endpoint.
Outcome measures
| Measure |
Bevacizumab and Erlotinib Hydrochloride
n=49 Participants
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.
|
|---|---|
|
Number of Confirmed Tumor Responses.
Partial Response (PR)
|
6 participants
|
|
Number of Confirmed Tumor Responses.
Complete Response (CR)
|
0 participants
|
SECONDARY outcome
Timeframe: From registration to death due to any cause, assessed up to 3 yearsEstimated using the method of Kaplan-Meier (1958).
Outcome measures
| Measure |
Bevacizumab and Erlotinib Hydrochloride
n=53 Participants
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.
|
|---|---|
|
Survival Time
|
9.9 months
Interval 7.2 to 13.6
|
SECONDARY outcome
Timeframe: From registration to documentation of disease progression, assessed up to 3 yearsEstimated using the method of Kaplan-Meier (1958).
Outcome measures
| Measure |
Bevacizumab and Erlotinib Hydrochloride
n=53 Participants
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.
|
|---|---|
|
Time to Disease Progression
|
4.4 months
Interval 3.0 to 7.8
|
SECONDARY outcome
Timeframe: From 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, assessed up to 3 yearsPopulation: There were 6 patients with a confirmed Partial Response.
Point estimates and 95% confidence intervals were calculated using the method of Duffy and Santner (1987).
Outcome measures
| Measure |
Bevacizumab and Erlotinib Hydrochloride
n=6 Participants
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.
|
|---|---|
|
Duration of Response
|
8.4 months
Interval 6.0 to 11.7
|
Adverse Events
Bevacizumab and Erlotinib Hydrochloride
Serious events: 22 serious events
Other events: 54 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bevacizumab and Erlotinib Hydrochloride
n=55 participants at risk
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Tumor tissue and blood specimens are collected periodically for correlative studies. Specimens are examined by immunohistochemistry for epidermal growth factor receptor (EGFR) and P-EGFR protein levels; AKT p-AKT, mitogen-activated protein kinase (MAPK) and P-MAPK protein levels; and vascular endothelial growth factor receptor (VEGFR)-1 and VEGFR-2 protein levels. EGFR mutations are detected by laser capture microdissection. Enzyme-linked immunosorbent assay is used to measure total and free serum VEGF levels.
|
|---|---|
|
Cardiac disorders
Sinus tachycardia
|
1.8%
1/55 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
7.3%
4/55 • Number of events 4
|
|
Gastrointestinal disorders
Constipation
|
1.8%
1/55 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
3.6%
2/55 • Number of events 2
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
1.8%
1/55 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
1.8%
1/55 • Number of events 1
|
|
General disorders
Disease progression
|
1.8%
1/55 • Number of events 1
|
|
General disorders
Fever
|
1.8%
1/55 • Number of events 1
|
|
General disorders
Pain
|
1.8%
1/55 • Number of events 1
|
|
General disorders
Sudden death
|
1.8%
1/55 • Number of events 1
|
|
Hepatobiliary disorders
Cholecystitis
|
1.8%
1/55 • Number of events 1
|
|
Hepatobiliary disorders
Hepatobiliary disease
|
1.8%
1/55 • Number of events 1
|
|
Infections and infestations
Biliary tract infection
|
5.5%
3/55 • Number of events 3
|
|
Infections and infestations
Infection
|
3.6%
2/55 • Number of events 2
|
|
Infections and infestations
Sepsis
|
1.8%
1/55 • Number of events 1
|
|
Investigations
Alanine aminotransferase increased
|
1.8%
1/55 • Number of events 1
|
|
Investigations
Alkaline phosphatase increased
|
3.6%
2/55 • Number of events 2
|
|
Investigations
Aspartate aminotransferase increased
|
1.8%
1/55 • Number of events 1
|
|
Investigations
Blood bilirubin increased
|
1.8%
1/55 • Number of events 1
|
|
Investigations
INR increased
|
1.8%
1/55 • Number of events 1
|
|
Investigations
Platelet count decreased
|
1.8%
1/55 • Number of events 1
|
|
Investigations
Weight loss
|
3.6%
2/55 • Number of events 2
|
|
Metabolism and nutrition disorders
Serum sodium decreased
|
1.8%
1/55 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
1.8%
1/55 • Number of events 1
|
|
Nervous system disorders
Headache
|
1.8%
1/55 • Number of events 1
|
|
Nervous system disorders
Ischemia cerebrovascular
|
1.8%
1/55 • Number of events 1
|
|
Renal and urinary disorders
Renal failure
|
1.8%
1/55 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
3.6%
2/55 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
1.8%
1/55 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hemorrhage
|
1.8%
1/55 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
1.8%
1/55 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
1.8%
1/55 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash desquamating
|
1.8%
1/55 • Number of events 1
|
|
Vascular disorders
Hypertension
|
1.8%
1/55 • Number of events 1
|
|
Vascular disorders
Hypotension
|
1.8%
1/55 • Number of events 1
|
|
Vascular disorders
Thrombosis
|
1.8%
1/55 • Number of events 1
|
Other adverse events
| Measure |
Bevacizumab and Erlotinib Hydrochloride
n=55 participants at risk
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Tumor tissue and blood specimens are collected periodically for correlative studies. Specimens are examined by immunohistochemistry for epidermal growth factor receptor (EGFR) and P-EGFR protein levels; AKT p-AKT, mitogen-activated protein kinase (MAPK) and P-MAPK protein levels; and vascular endothelial growth factor receptor (VEGFR)-1 and VEGFR-2 protein levels. EGFR mutations are detected by laser capture microdissection. Enzyme-linked immunosorbent assay is used to measure total and free serum VEGF levels.
|
|---|---|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
18.2%
10/55 • Number of events 28
|
|
Blood and lymphatic system disorders
Hemolysis
|
1.8%
1/55 • Number of events 2
|
|
Cardiac disorders
Atrial fibrillation
|
1.8%
1/55 • Number of events 1
|
|
Eye disorders
Cataract
|
1.8%
1/55 • Number of events 1
|
|
Eye disorders
Conjunctivitis
|
1.8%
1/55 • Number of events 2
|
|
Eye disorders
Dry eye syndrome
|
3.6%
2/55 • Number of events 3
|
|
Eye disorders
Eye disorder
|
5.5%
3/55 • Number of events 7
|
|
Eye disorders
Keratitis
|
1.8%
1/55 • Number of events 1
|
|
Eye disorders
Vision blurred
|
1.8%
1/55 • Number of events 2
|
|
Eye disorders
Watering eyes
|
1.8%
1/55 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
23.6%
13/55 • Number of events 25
|
|
Gastrointestinal disorders
Anal pain
|
1.8%
1/55 • Number of events 2
|
|
Gastrointestinal disorders
Ascites
|
1.8%
1/55 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
18.2%
10/55 • Number of events 27
|
|
Gastrointestinal disorders
Diarrhea
|
43.6%
24/55 • Number of events 106
|
|
Gastrointestinal disorders
Dyspepsia
|
9.1%
5/55 • Number of events 6
|
|
Gastrointestinal disorders
Ear, nose and throat examination abnormal
|
1.8%
1/55 • Number of events 1
|
|
Gastrointestinal disorders
Flatulence
|
1.8%
1/55 • Number of events 2
|
|
Gastrointestinal disorders
Gastic fistula
|
1.8%
1/55 • Number of events 1
|
|
Gastrointestinal disorders
Mucositis oral
|
25.5%
14/55 • Number of events 18
|
|
Gastrointestinal disorders
Nausea
|
30.9%
17/55 • Number of events 43
|
|
Gastrointestinal disorders
Oral hemorrhage
|
1.8%
1/55 • Number of events 1
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
1.8%
1/55 • Number of events 1
|
|
Gastrointestinal disorders
Stomach pain
|
1.8%
1/55 • Number of events 3
|
|
Gastrointestinal disorders
Vomiting
|
14.5%
8/55 • Number of events 12
|
|
General disorders
Chest pain
|
1.8%
1/55 • Number of events 1
|
|
General disorders
Chills
|
5.5%
3/55 • Number of events 5
|
|
General disorders
Edema limbs
|
1.8%
1/55 • Number of events 1
|
|
General disorders
Fatigue
|
58.2%
32/55 • Number of events 137
|
|
General disorders
Fever
|
3.6%
2/55 • Number of events 2
|
|
General disorders
General symptom
|
1.8%
1/55 • Number of events 1
|
|
General disorders
Pain
|
3.6%
2/55 • Number of events 3
|
|
Hepatobiliary disorders
Gallbladder obstruction
|
1.8%
1/55 • Number of events 1
|
|
Infections and infestations
Colitis, infectious (e.g., Clostridium difficile)
|
1.8%
1/55 • Number of events 1
|
|
Infections and infestations
Gallbladder infection
|
1.8%
1/55 • Number of events 1
|
|
Infections and infestations
Infection
|
1.8%
1/55 • Number of events 1
|
|
Infections and infestations
Nail infection
|
1.8%
1/55 • Number of events 1
|
|
Infections and infestations
Sinusitis
|
1.8%
1/55 • Number of events 1
|
|
Infections and infestations
Tooth infection
|
1.8%
1/55 • Number of events 1
|
|
Infections and infestations
Upper respiratory infection
|
1.8%
1/55 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
1.8%
1/55 • Number of events 1
|
|
Infections and infestations
Vaginal infection
|
1.8%
1/55 • Number of events 1
|
|
Infections and infestations
Wound infection
|
3.6%
2/55 • Number of events 2
|
|
Investigations
Alanine aminotransferase increased
|
20.0%
11/55 • Number of events 17
|
|
Investigations
Alkaline phosphatase increased
|
20.0%
11/55 • Number of events 29
|
|
Investigations
Aspartate aminotransferase increased
|
29.1%
16/55 • Number of events 26
|
|
Investigations
Blood bilirubin increased
|
29.1%
16/55 • Number of events 20
|
|
Investigations
Creatinine increased
|
3.6%
2/55 • Number of events 2
|
|
Investigations
Leukocyte count decreased
|
9.1%
5/55 • Number of events 8
|
|
Investigations
Lymphocyte count decreased
|
1.8%
1/55 • Number of events 2
|
|
Investigations
Neutrophil count decreased
|
1.8%
1/55 • Number of events 2
|
|
Investigations
Platelet count decreased
|
14.5%
8/55 • Number of events 52
|
|
Investigations
Weight gain
|
1.8%
1/55 • Number of events 1
|
|
Investigations
Weight loss
|
20.0%
11/55 • Number of events 17
|
|
Metabolism and nutrition disorders
Anorexia
|
38.2%
21/55 • Number of events 45
|
|
Metabolism and nutrition disorders
Blood glucose increased
|
18.2%
10/55 • Number of events 18
|
|
Metabolism and nutrition disorders
Dehydration
|
9.1%
5/55 • Number of events 5
|
|
Metabolism and nutrition disorders
Serum albumin decreased
|
20.0%
11/55 • Number of events 24
|
|
Metabolism and nutrition disorders
Serum calcium decreased
|
3.6%
2/55 • Number of events 2
|
|
Metabolism and nutrition disorders
Serum calcium increased
|
1.8%
1/55 • Number of events 3
|
|
Metabolism and nutrition disorders
Serum glucose decreased
|
1.8%
1/55 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum magnesium increased
|
1.8%
1/55 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum potassium decreased
|
1.8%
1/55 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum potassium increased
|
3.6%
2/55 • Number of events 4
|
|
Metabolism and nutrition disorders
Serum sodium decreased
|
10.9%
6/55 • Number of events 8
|
|
Metabolism and nutrition disorders
Serum sodium increased
|
1.8%
1/55 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
1.8%
1/55 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.5%
3/55 • Number of events 8
|
|
Musculoskeletal and connective tissue disorders
Joint disorder
|
1.8%
1/55 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.5%
3/55 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
1.8%
1/55 • Number of events 2
|
|
Nervous system disorders
Dizziness
|
1.8%
1/55 • Number of events 2
|
|
Nervous system disorders
Dysgeusia
|
9.1%
5/55 • Number of events 14
|
|
Nervous system disorders
Headache
|
9.1%
5/55 • Number of events 5
|
|
Nervous system disorders
Ischemia cerebrovascular
|
1.8%
1/55 • Number of events 1
|
|
Nervous system disorders
Neurological disorder NOS
|
5.5%
3/55 • Number of events 6
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
1.8%
1/55 • Number of events 1
|
|
Psychiatric disorders
Anxiety
|
5.5%
3/55 • Number of events 8
|
|
Psychiatric disorders
Confusion
|
1.8%
1/55 • Number of events 1
|
|
Psychiatric disorders
Depression
|
1.8%
1/55 • Number of events 5
|
|
Psychiatric disorders
Insomnia
|
5.5%
3/55 • Number of events 9
|
|
Renal and urinary disorders
Glomerular filtration rate decreased
|
1.8%
1/55 • Number of events 1
|
|
Renal and urinary disorders
Hemoglobin urine positive
|
3.6%
2/55 • Number of events 2
|
|
Renal and urinary disorders
Proteinuria
|
9.1%
5/55 • Number of events 7
|
|
Renal and urinary disorders
Urogenital disorder
|
1.8%
1/55 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.5%
3/55 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
3.6%
2/55 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
9.1%
5/55 • Number of events 11
|
|
Respiratory, thoracic and mediastinal disorders
Voice alteration
|
1.8%
1/55 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
10.9%
6/55 • Number of events 49
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
29.1%
16/55 • Number of events 51
|
|
Skin and subcutaneous tissue disorders
Hand-and-foot syndrome
|
1.8%
1/55 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
12.7%
7/55 • Number of events 36
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
7.3%
4/55 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
18.2%
10/55 • Number of events 16
|
|
Skin and subcutaneous tissue disorders
Rash desquamating
|
76.4%
42/55 • Number of events 203
|
|
Skin and subcutaneous tissue disorders
Skin disorder
|
1.8%
1/55 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
1.8%
1/55 • Number of events 1
|
|
Vascular disorders
Hypertension
|
29.1%
16/55 • Number of events 45
|
|
Vascular disorders
Hypotension
|
1.8%
1/55 • Number of events 1
|
|
Vascular disorders
Thrombosis
|
1.8%
1/55 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60