A Phase II Pilot Study of Preoperative Gemcitabine and Bevacizumab-Based Chemoradiation for Patients With Resectable Adenocarcinoma of the Pancreas
18 Years
N/A
Both
Pancreatic Neoplasms
Trial Information
A Phase II Pilot Study of Preoperative Gemcitabine and Bevacizumab-Based Chemoradiation for Patients With Resectable Adenocarcinoma of the Pancreas
Gemcitabine is designed to disrupt the growth of the cancer cells, which causes the cancer
cells to start to die.
Avastin is designed to prevent or slow down the growth of tumors by its damaging effects on
blood vessel growth in tumors.
Before treatment starts, you will have a complete physical exam. Blood (about 2
tablespoons) will be drawn for tests, and a urine test will be performed. Chest x-rays and
computed tomography (CT) scans of the abdomen will be done. Women who are able to have
children must have a negative blood (1-2 tablespoons) pregnancy test.
If you are found to be eligible to take part in this study, you will receive gemcitabine
once a week, Avastin once every 2 weeks, and radiation 5 times a week. Gemcitabine and
Avastin will be given on Saturdays, and the radiation will be given Monday through Friday of
each week. You will receive this treatment as an outpatient for 6 weeks.
You will receive gemcitabine through a needle in a vein on Days 1, 8, 15, 22, 29, and 36
(+/- 2 days). You will receive Avastin through a needle in a vein every 2 weeks on Days 1,
15, and 29 (+/- 2 days). On the days you receive both drugs, you will receive Avastin over
30-90 minutes and gemcitabine over 40 minutes.
The first dose of Avastin will be given over about 90 minutes. If you do not have a
reaction (such as fever/chills), the next dose will be given over about 60 minutes, and if
again no reaction occurs, each dose after that will be given over about 30 minutes. If you
experience a reaction to the Avastin infusion, you may be given acetaminophen (such as
Tylenol) by mouth and/or diphenhydramine (Benadryl) by vein over 30 minutes before each dose
to decrease the risk of further reactions.
Radiation will be given Monday through Friday for 5 1/2 weeks. Each day of treatment, you
will lie on a treatment table. The radiation therapist will help position your body so that
the radiation goes to the right place. A machine will deliver the radiation. It will take
about 15-20 minutes to receive the radiation treatment each day.
If any days of radiation are missed, these days will be made up at the end of your treatment
(at the end of 28 days) so that you receive the full amount of radiation.
During the study, you will have physical exams weekly while you are receiving
chemoradiation, every other week while you are receiving chemotherapy after surgery, and
every 4 months during the follow-up period. You will have blood drawn (1-2 tablespoons each
time) for routine tests on a weekly basis while you are receiving chemoradiation, every
other week while you are taking Avastin after surgery for 3 months, and every 4 months
during the follow-up period. The possible development of side effects will be closely
monitored and could require extra blood and/or urine samples. You may also have physical
exams, blood and urine tests, x-rays, and scans after completing the chemoradiation part of
the study, depending upon what is medically needed for evaluation of ongoing therapy.
The overall effect of treatment will be evaluated at least 8 weeks (+/- 2 days) after the
completion of chemoradiation. A chest x-ray and CT scans of the chest, abdomen, and pelvis
will then be performed, and blood (about 2 tablespoons) will be drawn for routine tests.
Some participants will have surgery to remove part of the pancreas, if needed. The reason
to wait at least 8 weeks is to allow a safe period of time to pass after the last dose of
Avastin to prevent bleeding during surgery. It may also help decrease the risk of
postoperative complications, including bleeding and poor wound healing.
This research study allows participants to receive up to 3 infusions of Avastin during the
chemoradiation part of the study. If the treatment is shown to benefit you, your doctor may
continue to give additional infusions of Avastin every 2 weeks (+/- 2 days) for 3 months
after surgery. After the Avastin treatment, you will have a chest x-ray, abdominal CT scan,
and blood (about 2 tablespoons) will be drawn for routine tests every 4 months after surgery
for 2 years to check the status of the tumor.
This is an investigational study. The study drugs are commercially available and FDA
approved, but their use together with radiation is experimental. Avastin is FDA approved
for colon and lung cancers but has not been evaluated by the FDA for pancreatic cancer.
Gemcitabine is FDA approved for pancreatic cancer. Avastin will be provided free of
charge during the study, however the cost of the infusion of the drug will be the
responsibility of you and/or your insurance company. The costs of gemcitabine and radiation
are considered standard of care, and will be the responsibility of you and/or your insurance
company. Up to 31 patients will take part in this study. All will be enrolled at M. D.
Anderson.
Inclusion Criteria:
1. Cytologic or histologic proof of adenocarcinoma of the pancreatic head or uncinate
process is required prior to treatment. Islet cell tumors are not eligible.
2. Patients must be staged with a physical exam, CXR, and contrast-enhanced CT. Only
potentially resectable patients are eligible. Potentially resectable defined as: a)
no extra pancreatic disease, b) no evidence (on CT) of tumor extension to the celiac
axis or SMA, and c) no evidence (CT or angiogram) of occlusion of the SMV or SMPV
confluence. Visceral angiography is optional. Laparoscopic staging is not part of the
pretreatment evaluation for this study. Laparoscopy may be performed prior to planned
laparotomy at surgeon's discretion. Staging needs to be done within 28 days of
enrollment.
3. Patients cannot have known hepatic or peritoneal metastases detected by ultrasound
(US), CT scan, or laparotomy prior to chemoradiation.
4. There will be no upper age restriction; patients with Karnofsky performance status
greater than 70 are eligible.
5. Adequate renal, and bone marrow function: Leukocytes greater than or equal to
3,000/uL; Absolute neutrophil count greater than or equal to 1,500/uL; Platelets
greater than or equal to 100,000/U1; Serum creatinine less than or equal to 2.0-mg/dL
and urine protein: creatinine ratio less than or equal to 1.0 at screening
6. Hepatic function (endoscopic or percutaneous drainage as needed) Total bilirubin less
than or equal to 2 X institutional upper limits of normal (ULN); AST (SGOT)/ALT
(SGPT) less than or equal to 5 X institutional ULN
7. Patients must have no fever or evidence of infection or other coexisting medical
condition that would preclude protocol therapy.
8. Pregnant women with a positive (blood B-HCG) pregnancy test are excluded from this
study; women of childbearing potential (defined as those who have not undergone a
hysterectomy or who have not been postmenopausal for at least 24 consecutive months)
must agree to practice adequate contraception and to refrain from breast feeding, as
specified in the informed consent.
9. Patients must sign a study-specific consent form.
Exclusion Criteria:
1. Tumors in the body or tail of the pancreas (to the left of the portal -SMV
confluence) are not eligible.
2. Patients with uncontrolled hypertension, baseline blood pressure of greater than
150/100 mmHg
3. Unstable angina or New York Heart Association (NYHA) Grade II or greater congestive
heart failure.
4. History of myocardial infarction, stroke, DVT, or pulmonary embolism within 6 months
of the study
5. Clinically significant peripheral vascular disease.
6. Known history of bleeding diathesis coagulopathy. If patient has prior documented PT,
INR then INR should be less than 2.0 (patients on anticoagulation for atrial
fibrillation, other cardiac disorders, and for remote history of thrombosis are not
excluded). Lab results should be within 2 weeks of patient enrollment.
7. Known presence of central nervous system or brain metastases.
8. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 0, anticipation of need for major surgical procedure during the course
of the study
9. Minor surgical procedures such as fine needle aspirations or core biopsies within 7
days prior to Day 0
10. Urine protein: creatinine ratio greater than 1.0 at screening; a 24 hour urine
protein should be obtained and the level must be less than 1gm/24 hours in order for
the patient to be eligible.
11. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to Day 0
12. Serious, non-healing wound, ulcer, or bone fracture
13. Evidence of duodenal invasion
14. Inability to comply with study and/or follow-up procedures
15. Patients less than 18 years of age.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Number of Patients with Resection
Outcome Time Frame:
8 weeks (+/- 2 days) after the completion of chemoradiation
Safety Issue:
No
Principal Investigator
Douglas Evans, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
2005-0784
NCT ID:
NCT00336648
Start Date:
June 2006
Completion Date:
July 2008
Related Keywords:
- Pancreatic Neoplasms
- Pancreatic Neoplasms
- Bevacizumab
- Gemcitabine
- Radiation Therapy
- adenocarcinoma of the pancreatic head
- adenocarcinoma of the uncinate process
- Adenocarcinoma
- Neoplasms
- Pancreatic Neoplasms
Name | Location |
|---|---|
| U.T. M.D. Anderson Cancer Center | Houston, Texas 77030 |
