Pancreatic Cancer
Conditions
Keywords
Advanced Pancreatic Cancer
Brief summary
This is a phase II study of biweekly (every other week) bevacizumab followed by gemcitabine then infusional 5-fluorouracil in patients with stage III or IV pancreatic cancer. Patients' response will be evaluated every 8 weeks using usual CT scanning techniques. RECIST (Response Evaluation Criteria in Solid tumors) criteria will be applied to evaluate response. Tumor marker levels (Ca 19-9) will be assessed every 4 weeks, but will not be used to measure response.
Detailed description
Rationale: Research indicates that the vascular endothelial growth factor (VEGF), or a substance made by cells that stimulates new blood vessel formation, plays an important role in the growth and metastasis of many cancers, including pancreatic carcinoma. Both VEGF and its receptors are overexpressed in pancreatic cancer. Bevacizumab works by blocking VEGF and the growth of cancer cells in the process. The current study combines bevacizumab with two commonly used pancreatic cancer drugs, gemcitabine and infusional 5-FU. Previous studies indicate that bevacizumab combined with other anti-cancer drugs such as 5-FU improves patient survival. In addition, other research suggests that the drug administration schedule of the current study may improve patient outcomes compared to other types of administration and sequencing. Purpose: The primary objective of this study is to assess the rate of progression free survival at 6 months in patients with advanced pancreatic cancer given gemcitabine, infusional 5-FU, and bevacizumab. Secondary objectives of this study include measuring response rates, 6 month and 1-year survival rates, and median overall survival. Treatment: Study participants will be given bevacizumab, gemcitabine, and 5-FU. These drugs will be administered through intravenous infusions in that order every other week on days 1 and 15. Treatments will be given in 28-day cycles. Participants will therefore receive study drugs during weeks 1 and 3, and then receive no study drugs during weeks 2 and 4. Imaging exams will be performed every 8 weeks to assess disease size. Several other tests will be given throughout the study to closely monitor patients. Tumor level markers will be assessed every 4 weeks, but will not be used to measure response. Study treatments will be discontinued due to disease growth or severe adverse effects.
Interventions
DRUGGemcitabine
1000 mg/m2 over 100 minutes every 2 weeks.
DRUGBevacizumab
10 mg/kg every 2 weeks.
2400 mg/m2 over 48 hours every 2 weeks.
Sponsors
Genentech, Inc.
Tony Bekaii-Saab
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
* Males or females age \>=18 years. * Established histological confirmation of adenocarcinoma of the pancreas. * Stage III and stage IV will be allowed.
Exclusion criteria
* No prior chemotherapy or radiotherapy allowed except for that given as part of an adjuvant regimen if \>4 weeks have elapsed since the end of therapy. Any prior treatment with antibodies to VEGF. * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to starting the study. * Pregnant or lactating women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Rate of Progression Free Survival at 6 Months (24 Weeks) From Initiation of Therapy | 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rates Defined by RECIST 1.0 | 6 months | The National Cancer Institutes Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 was used in accessing response for patients |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab Gemcitabine : 1000 mg/m2 over 100 minutes every 2 weeks.
Bevacizumab : 10 mg/kg every 2 weeks.
Infusional 5-Fluorouracil : 2400 mg/m2 over 48 hours every 2 weeks. | 42 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Non compliance unrelated to toxicity | 1 |
| Overall Study | Treatment -related toxicity | 2 |
Baseline characteristics
| Characteristic | Bevacizumab |
|---|---|
| Age, Continuous | 60 years |
| Albumin Low (<3.4 g/dl) | 14 participants |
| Albumin Normal (≥3.4 g/dl) | 28 participants |
| CA19-9 (tumor marker levels) Elevated (>37 U/ml) | 36 participants |
| CA19-9 (tumor marker levels) Normal (≤37 U/ml) | 6 participants |
| Disease stage III (Unresectable primary tumor) | 2 participants |
| Disease stage IV (Cancer has spread o distant tissue or organ) | 40 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance status 0 (Fully Active) | 15 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance status 1 (Restricted in physical activity) | 27 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Prior adjuvant therapy Chemoraditation | 1 participants |
| Prior adjuvant therapy Gemcitabine-based | 1 participants |
| Prior adjuvant therapy No prior adjuvant therapy | 40 participants |
| Region of Enrollment United States | 42 participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 19 Participants |
| Site of metastasis Liver only | 29 participants |
| Site of metastasis Liver+other | 2 participants |
| Site of metastasis Other only | 9 participants |
| Site of metastasis Recurrent metastatic disease | 2 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 42 / 42 |
| serious Total, serious adverse events | 1 / 42 |
Outcome results
Primary
Rate of Progression Free Survival at 6 Months (24 Weeks) From Initiation of Therapy
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab | Rate of Progression Free Survival at 6 Months (24 Weeks) From Initiation of Therapy | 49 percent of patients |
Secondary
Response Rates Defined by RECIST 1.0
The National Cancer Institutes Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 was used in accessing response for patients
Time frame: 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab | Response Rates Defined by RECIST 1.0 | Complete Respsonse | 0 patients |
| Bevacizumab | Response Rates Defined by RECIST 1.0 | Partial Response | 12 patients |
| Bevacizumab | Response Rates Defined by RECIST 1.0 | Stable Disease | 18 patients |
| Bevacizumab | Response Rates Defined by RECIST 1.0 | Progressive Disease | 10 patients |