Adenocarcinoma of the Pancreas, Pancreatic Cancer
Conditions
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.
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.
Interventions
DRUGBevacizumab
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.
DRUGErlotinib
Taken orally every day. Participants may continue to receive study treatment as long as there is no disease progression or serious side effects.
DRUGGemcitabine
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.
Sponsors
Genentech, Inc.
Beth Israel Deaconess Medical Center
Dana-Farber Cancer Institute
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| Overall Survival | 5 years | overall survival (OS) = time from study entry until death from any cause |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gemcitabine, Bevacizumab and Erlotinib 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. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | never began study therapy | 2 |
Baseline characteristics
| Characteristic | Gemcitabine, Bevacizumab and Erlotinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 13 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Age, Continuous | 61.6 years STANDARD_DEVIATION 9.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 28 Participants |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 30 / 30 |
| serious Total, serious adverse events | 11 / 30 |
Outcome results
Primary
Time to Tumor Progression
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
Population: participants who started treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gemcitabine, Bevacizumab and Erlotinib | Time to Tumor Progression | 3.5 months |
Secondary
Overall Survival
overall survival (OS) = time from study entry until death from any cause
Time frame: 5 years
Population: participants who started treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gemcitabine, Bevacizumab and Erlotinib | Overall Survival | 6.7 months |
Secondary
Response Rate
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
Population: participants with response data available
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Gemcitabine, Bevacizumab and Erlotinib | Response Rate | Partial Response | 1 Participants |
| Gemcitabine, Bevacizumab and Erlotinib | Response Rate | Progressive Disease | 8 Participants |
| Gemcitabine, Bevacizumab and Erlotinib | Response Rate | Stable Disease | 19 Participants |
Secondary
Toxicity Profile
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
Population: participants who started treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Gemcitabine, Bevacizumab and Erlotinib | Toxicity Profile | Lymphopenia | 1 Participants |
| Gemcitabine, Bevacizumab and Erlotinib | Toxicity Profile | Neutrophils | 4 Participants |
| Gemcitabine, Bevacizumab and Erlotinib | Toxicity Profile | ALT-SGPT | 3 Participants |
| Gemcitabine, Bevacizumab and Erlotinib | Toxicity Profile | Fatigue | 2 Participants |
| Gemcitabine, Bevacizumab and Erlotinib | Toxicity Profile | Leukocytes | 2 Participants |
| Gemcitabine, Bevacizumab and Erlotinib | Toxicity Profile | Rash: acne/acneiform | 2 Participants |
| Gemcitabine, Bevacizumab and Erlotinib | Toxicity Profile | Thrombosis/thrombus/embolism | 2 Participants |
| Gemcitabine, Bevacizumab and Erlotinib | Toxicity Profile | Anorexia | 1 Participants |
| Gemcitabine, Bevacizumab and Erlotinib | Toxicity Profile | AST - SGOT | 1 Participants |
| Gemcitabine, Bevacizumab and Erlotinib | Toxicity Profile | Hemoglobin | 1 Participants |
| Gemcitabine, Bevacizumab and Erlotinib | Toxicity Profile | Nonneuropathic generalized weakness | 1 Participants |
| Gemcitabine, Bevacizumab and Erlotinib | Toxicity Profile | Upper GI-hemorrhage NOS | 1 Participants |
| Gemcitabine, Bevacizumab and Erlotinib | Toxicity Profile | Vascular access-Thrombosis/embolism | 1 Participants |
| Gemcitabine, Bevacizumab and Erlotinib | Toxicity Profile | Vessel injury - artery - Other NOS | 1 Participants |
| Gemcitabine, Bevacizumab and Erlotinib | Toxicity Profile | Weight loss | 1 Participants |