Gemcitabine, Bevacizumab and Erlotinib in Pancreatic Cancer

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00366457
• Collaborator: Genentech, Inc. (Industry), Beth Israel Deaconess Medical Center (Other), Dana-Farber Cancer Institute (Other)
• Enrollment: 32
• Locations: 3
• Arm: 1
• Duration (Months): 59
• Patients Per Site: 10.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The main purpose of this study is to learn whether or not the combination of gemcitabine, bevacizumab and erlotinib works in treating patients with advanced or metastatic pancreatic cancer. Bevacizumab is a new anti-cancer drug. It is an antibody that works to slow or stop cell growth in cancerous tumors by decreasing the blood supply to the tumors. It is approved by the FDA for the treatment of colorectal cancer but is still considered investigational for treating pancreatic cancer.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer; Adenocarcinoma of the Pancreas	Drug: Bevacizumab; Drug: Erlotinib; Drug: Gemcitabine	Phase 2

Detailed Description

• Participants will receive study treatment as an outpatient. The study treatment will be given in time periods called cycles. Each treatment cycle will be 28 days.

• Gemcitabine will be given intravenously on days 1, 8, and 15 (once per week for the first three weeks) of the treatment cycle.

• Bevacizumab will be given intravenously on days 1 and 15 (once every 2 weeks) of the treatment cycle.

• Erlotinib will be taken orally every day of the treatment cycle.

• Participants will see the doctor or nurse practitioner every week for the first 28 days of treatment. During all of the following cycles, they will see the doctor or nurse practitioner on day 1 and day 15 of each cycle.

• Each 4-week cycle can be repeated until the participant or the doctor decided that they should be removed from the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Gemcitabine, Bevacizumab and Erlotinib in Locally Advanced and Metastatic Pancreatic Cancer
• Study Start Date: Aug 1, 2006
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Jul 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Other: Gemcitabine, Bevacizumab and Erlotinib single-arm, no masking

Drug: Bevacizumab; Given intravenously on days 1 and 25 of every 28-day cycle (one every 2 weeks). Participants may continue to receive study treatment as long as there is no disease progression or serious side effects.; Other Names: rhuMAb VEGF ; Drug: Erlotinib; Taken orally every day. Participants may continue to receive study treatment as long as there is no disease progression or serious side effects.; Other Names: Tarceva ; Drug: Gemcitabine; Given intravenously on days 1, 8 and 15 of each 28-day cycle. Participants may continue to receive study treatment as long as there is no disease progression or serious side effects.; Other Names: Gemzar

Outcome Measures

Primary Outcome Measures

1. Time to Tumor Progression [all patients will be followed for a minimum of 4 months]

   Time to tumor progression (TTP) = time from date of initial treatment to first objective documentation of progressive disease or death; patients who die without a reported prior progression will be considered to have progressed on the day of their death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Secondary Outcome Measures

1. Response Rate [after at least one 28-day cycle of treatment]

   Response rate using RECIST criteria and latest time point available. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

2. Toxicity Profile [during and after first 28-day cycle of treatment]

   Grade 3-4 treatment-related toxicities (treatment-related = possible, probable, or definite) Grading system: 1= mild, 2 = moderate, 3 = severe, 4 = life-threatening

3. Overall Survival [5 years]

   overall survival (OS) = time from study entry until death from any cause

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Previously untreated patients with unresectable or metastatic adenocarcinoma of the pancreas

• ECOG Performance Status 0-2

• 18 years of age or older

• Radiographically measurable disease

• Expected survival of at least 4 months

• Creatinine of </= 2.0

• Adequate hepatic function

• Adequate hematopoietic function

• Use of effective means of contraception in subjects of child-bearing potential

Exclusion Criteria:

• Warfarin anticoagulation

• Prior treatment with a tyrosine kinase inhibitor, EGFR inhibitor, or VEGF inhibitor

• Coexistent malignant disease

• Current or recent (within 4 weeks) participation in a clinical trial

• Pregnancy

• Documented invasion of adjacent organs or major blood vessels

• Blood pressure of > 150/100mmHg

• Unstable angina

• NYHA Grade II or greater congestive heart failure

• History of myocardial infarction or stroke within 6 months

• Clinically significant peripheral vascular disease

• Evidence of bleeding diathesis of coagulopathy

• Presence of CNS or brain metastases

• Major surgical procedure, open biopsy, or significant traumatic event within 28 days

• Minor surgical procedures, fine needle aspirations or core biopsies within 7 days

• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months

• Serious non-healing wound, ulcer or bone fracture

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Massachusetts General Hospital
• Genentech, Inc.
• Beth Israel Deaconess Medical Center
• Dana-Farber Cancer Institute

Investigators

• Principal Investigator: Lawrence S. Blaszkowsky, MD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Lawrence S. Blaszkowsky, MD, Assistant Physician, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00366457
• Other Study ID Numbers: 05-234
• First Posted: Aug 21, 2006
• Last Update Posted: May 15, 2017
• Last Verified: Apr 1, 2017

• Additional relevant MeSH terms: Pancreatic Neoplasms; Gemcitabine; Bevacizumab; Erlotinib Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Gemcitabine, Bevacizumab and Erlotinib
Arm/Group Description	single-arm, no masking Bevacizumab: Given intravenously on days 1 and 25 of every 28-day cycle (one every 2 weeks). Participants may continue to receive study treatment as long as there is no disease progression or serious side effects. Erlotinib: Taken orally every day. Participants may continue to receive study treatment as long as there is no disease progression or serious side effects. Gemcitabine: Given intravenously on days 1, 8 and 15 of each 28-day cycle. Participants may continue to receive study treatment as long as there is no disease progression or serious side effects.
Period Title: Overall Study
STARTED	32
COMPLETED	30
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Gemcitabine, Bevacizumab and Erlotinib
Arm/Group Description	single-arm, no masking Bevacizumab: Given intravenously on days 1 and 25 of every 28-day cycle (one every 2 weeks). Participants may continue to receive study treatment as long as there is no disease progression or serious side effects. Erlotinib: Taken orally every day. Participants may continue to receive study treatment as long as there is no disease progression or serious side effects. Gemcitabine: Given intravenously on days 1, 8 and 15 of each 28-day cycle. Participants may continue to receive study treatment as long as there is no disease progression or serious side effects.
Overall Participants	30
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	17 56.7%
>=65 years	13 43.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.6 (9.8)
Sex: Female, Male (Count of Participants)
Female	11 36.7%
Male	19 63.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	25 83.3%
Unknown or Not Reported	5 16.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	28 93.3%
More than one race	0 0%
Unknown or Not Reported	2 6.7%
Region of Enrollment (participants) [Number]
United States	30 100%

Outcome Measures

1. Primary Outcome

Title	Time to Tumor Progression
Description	Time to tumor progression (TTP) = time from date of initial treatment to first objective documentation of progressive disease or death; patients who die without a reported prior progression will be considered to have progressed on the day of their death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	all patients will be followed for a minimum of 4 months

Outcome Measure Data

Analysis Population Description

participants who started treatment

Arm/Group Title	Gemcitabine, Bevacizumab and Erlotinib
Arm/Group Description	single-arm, no masking Bevacizumab: Given intravenously on days 1 and 25 of every 28-day cycle (one every 2 weeks). Participants may continue to receive study treatment as long as there is no disease progression or serious side effects. Erlotinib: Taken orally every day. Participants may continue to receive study treatment as long as there is no disease progression or serious side effects. Gemcitabine: Given intravenously on days 1, 8 and 15 of each 28-day cycle. Participants may continue to receive study treatment as long as there is no disease progression or serious side effects.
Measure Participants	30
Median (95% Confidence Interval) [months]	3.5

2. Secondary Outcome

Title	Response Rate
Description	Response rate using RECIST criteria and latest time point available. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	after at least one 28-day cycle of treatment

Outcome Measure Data

Analysis Population Description

participants with response data available

Arm/Group Title	Gemcitabine, Bevacizumab and Erlotinib
Arm/Group Description	single-arm, no masking Bevacizumab: Given intravenously on days 1 and 25 of every 28-day cycle (one every 2 weeks). Participants may continue to receive study treatment as long as there is no disease progression or serious side effects. Erlotinib: Taken orally every day. Participants may continue to receive study treatment as long as there is no disease progression or serious side effects. Gemcitabine: Given intravenously on days 1, 8 and 15 of each 28-day cycle. Participants may continue to receive study treatment as long as there is no disease progression or serious side effects.
Measure Participants	28
Partial Response	1 3.3%
Progressive Disease	8 26.7%
Stable Disease	19 63.3%

3. Secondary Outcome

Title	Toxicity Profile
Description	Grade 3-4 treatment-related toxicities (treatment-related = possible, probable, or definite) Grading system: 1= mild, 2 = moderate, 3 = severe, 4 = life-threatening
Time Frame	during and after first 28-day cycle of treatment

Outcome Measure Data

Analysis Population Description

participants who started treatment

Arm/Group Title	Gemcitabine, Bevacizumab and Erlotinib
Arm/Group Description	single-arm, no masking Bevacizumab: Given intravenously on days 1 and 25 of every 28-day cycle (one every 2 weeks). Participants may continue to receive study treatment as long as there is no disease progression or serious side effects. Erlotinib: Taken orally every day. Participants may continue to receive study treatment as long as there is no disease progression or serious side effects. Gemcitabine: Given intravenously on days 1, 8 and 15 of each 28-day cycle. Participants may continue to receive study treatment as long as there is no disease progression or serious side effects.
Measure Participants	30
Neutrophils	4 13.3%
ALT-SGPT	3 10%
Fatigue	2 6.7%
Leukocytes	2 6.7%
Rash: acne/acneiform	2 6.7%
Thrombosis/thrombus/embolism	2 6.7%
Anorexia	1 3.3%
AST - SGOT	1 3.3%
Hemoglobin	1 3.3%
Lymphopenia	1 3.3%
Nonneuropathic generalized weakness	1 3.3%
Upper GI-hemorrhage NOS	1 3.3%
Vascular access-Thrombosis/embolism	1 3.3%
Vessel injury - artery - Other NOS	1 3.3%
Weight loss	1 3.3%

4. Secondary Outcome

Title	Overall Survival
Description	overall survival (OS) = time from study entry until death from any cause
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

participants who started treatment

Arm/Group Title	Gemcitabine, Bevacizumab and Erlotinib
Arm/Group Description	single-arm, no masking Bevacizumab: Given intravenously on days 1 and 25 of every 28-day cycle (one every 2 weeks). Participants may continue to receive study treatment as long as there is no disease progression or serious side effects. Erlotinib: Taken orally every day. Participants may continue to receive study treatment as long as there is no disease progression or serious side effects. Gemcitabine: Given intravenously on days 1, 8 and 15 of each 28-day cycle. Participants may continue to receive study treatment as long as there is no disease progression or serious side effects.
Measure Participants	30
Median (95% Confidence Interval) [months]	6.7

Adverse Events

Arm/Group Title	Gemcitabine, Bevacizumab and Erlotinib
Arm/Group Description	single-arm, no masking Bevacizumab: Given intravenously on days 1 and 25 of every 28-day cycle (one every 2 weeks). Participants may continue to receive study treatment as long as there is no disease progression or serious side effects. Erlotinib: Taken orally every day. Participants may continue to receive study treatment as long as there is no disease progression or serious side effects. Gemcitabine: Given intravenously on days 1, 8 and 15 of each 28-day cycle. Participants may continue to receive study treatment as long as there is no disease progression or serious side effects.
All Cause Mortality
	Gemcitabine, Bevacizumab and Erlotinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gemcitabine, Bevacizumab and Erlotinib
	Affected / at Risk (%)	# Events
Total	11/30 (36.7%)
Endocrine disorders
Death from disease progression	3/30 (10%)	3
Immune system disorders
Neutropenia	1/30 (3.3%)	1
Infections and infestations
Death from infection or sepsis	2/30 (6.7%)	2
Metabolism and nutrition disorders
Hyperbilirubinemia	1/30 (3.3%)	1
Nervous system disorders
Brain Infarct	1/30 (3.3%)	1
Respiratory, thoracic and mediastinal disorders
Pumonary embolism	4/30 (13.3%)	4
Hypoxia	1/30 (3.3%)	1
Other (Not Including Serious) Adverse Events
	Gemcitabine, Bevacizumab and Erlotinib
	Affected / at Risk (%)	# Events
Total	30/30 (100%)
Blood and lymphatic system disorders
Leukocytes	25/30 (83.3%)	84
Platelets	22/30 (73.3%)	80
Hemoglobin	21/30 (70%)	78
Neutrophils	21/30 (70%)	67
Lymphopenia	14/30 (46.7%)	30
Edema limb	5/30 (16.7%)	9
Cardiac disorders
Hypertension	5/30 (16.7%)	22
Eye disorders
Ocular-other	3/30 (10%)	3
Gastrointestinal disorders
Nausea	24/30 (80%)	73
Anorexia	19/30 (63.3%)	48
Constipation	17/30 (56.7%)	34
Diarrhea w/o prior colostomy	16/30 (53.3%)	61
Vomiting	15/30 (50%)	25
Muco/stomatitis (symptom) oral cavity	8/30 (26.7%)	9
Dehydration	7/30 (23.3%)	9
Muco/stomatitis by exam- oral cavity	6/30 (20%)	10
Flatulence	5/30 (16.7%)	10
GI-other	4/30 (13.3%)	7
Dyspepsia	3/30 (10%)	10
Taste disturbance	3/30 (10%)	3
Distention/bloating- abdominal	2/30 (6.7%)	6
Dry mouth	2/30 (6.7%)	2
General disorders
Fatigue	25/30 (83.3%)	102
Abdomen - pain	20/30 (66.7%)	47
Weight loss	15/30 (50%)	35
Rigors/chills	15/30 (50%)	20
Nose- hemorrhage	11/30 (36.7%)	19
Fever w/o neutropenia	11/30 (36.7%)	12
Insomnia	9/30 (30%)	14
Head/headache	6/30 (20%)	13
Extremity-limb- pain	6/30 (20%)	8
Muscle- pain	5/30 (16.7%)	5
Back- pain	4/30 (13.3%)	6
Chest/thoracic pain NOS	4/30 (13.3%)	4
Pain-other	3/30 (10%)	4
Throat/pharynx/larynx- pain	3/30 (10%)	4
Pain NOS	3/30 (10%)	3
Flu-like syndrome	2/30 (6.7%)	2
Joint- pain	2/30 (6.7%)	2
Rectum- hemorrhage	2/30 (6.7%)	2
Rectum- pain	2/30 (6.7%)	2
Sweating	2/30 (6.7%)	2
Immune system disorders
Allergic reaction	3/30 (10%)	4
Infections and infestations
Infection Gr0-2 neut- upper airway	4/30 (13.3%)	5
Metabolism and nutrition disorders
Hyperglycemia	23/30 (76.7%)	71
ALT- SGPT	22/30 (73.3%)	76
AST- SGOT	20/30 (66.7%)	77
Hyponatremia	17/30 (56.7%)	27
Alkaline phosphatase	13/30 (43.3%)	25
Bilirubin	10/30 (33.3%)	19
Hypoalbuminemia	9/30 (30%)	17
Hyperkalemia	6/30 (20%)	7
Proteinuria	5/30 (16.7%)	16
Hypocalcemia	5/30 (16.7%)	13
Bicarbonate	5/30 (16.7%)	6
Hypokalemia	5/30 (16.7%)	5
Hypoglycemia	3/30 (10%)	4
Hypomagnesemia	2/30 (6.7%)	2
Hypophosphatemia	2/30 (6.7%)	2
Musculoskeletal and connective tissue disorders
Nonneuropathic generalized weakness	3/30 (10%)	3
Arthritis	2/30 (6.7%)	4
Musculoskeletal/soft tissue-other	2/30 (6.7%)	2
Nervous system disorders
Depression	5/30 (16.7%)	11
Dizziness	4/30 (13.3%)	6
Neurologic-other	3/30 (10%)	6
Anxiety	3/30 (10%)	4
Neuropathy-sensory	2/30 (6.7%)	3
Renal and urinary disorders
Renal/GU-other	2/30 (6.7%)	2
Respiratory, thoracic and mediastinal disorders
Cough	9/30 (30%)	15
Dyspnea	6/30 (20%)	12
Voice changes/dysarthria	5/30 (16.7%)	8
Pulmonary/Upper Respiratory-other	3/30 (10%)	4
Allergic rhinitis	3/30 (10%)	3
Hiccoughs	2/30 (6.7%)	2
Skin and subcutaneous tissue disorders
Rash: acne/acneiform	23/30 (76.7%)	91
Rash/desquamation	9/30 (30%)	24
Pruritus/itching	7/30 (23.3%)	13
Skin-other	7/30 (23.3%)	12
Dry skin	6/30 (20%)	8
Alopecia	5/30 (16.7%)	23
Bruising	2/30 (6.7%)	2
Burn	2/30 (6.7%)	2
Vascular disorders
Thrombosis/thrombus/embolism	2/30 (6.7%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT 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.