Pancreatic CancerPhase 2NCT00602602
Bevacizumab, Combination Chemotherapy, and Radiation Therapy in Treating Patients Undergoing Surgery For Locally Advanced Pancreatic Cancer
A Phase 2 study testing bevacizumab, fluorouracil and gemcitabine hydrochloride in people with Pancreatic Cancer, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial summary
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Pancreatic Cancer
- What is being tested?
- bevacizumab, fluorouracil and gemcitabine hydrochloride
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2007to Sep 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed adenocarcinoma of the pancreas
- Resectable, marginally resectable, or unresectable disease determined by one of the following:
- Contrast-enhanced helical-CT scan
- Endoscopic ultrasound with biopsy (in patients who do not have metastatic or grossly unresectable disease)
- Dedicated pancreatic MRI
- Tumor must be locally advanced or potentially resectable, as determined by one of the following:
- Abutment of the portal or superior mesenteric veins, hepatic or superior mesenteric artery
- Extension to the origin of gastroduodenal artery
- Occlusion of the superior mesenteric vein for < 2 cm
- Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT
- Marker elevation alone not allowed as justification for study entry
- Formalin-fixed, paraffin-embedded tumor tissue specimens from prior biopsy or surgical resection allowed for correlative studies
- No known brain metastases or tumor metastatic to the peritoneum, liver, or other organs
PATIENT CHARACTERISTICS:
- ECOG performance status 0-1
- ANC ≥1,500/mm³
- Platelet count ≥ 100,000/mm³
- AST and ALT ≤ 2.5 times upper limit of normal (ULN)
- Creatinine < 1.5 times ULN
- Bilirubin < 2.0 mg/dL (≤ 10 mg/dL for patients with biliary obstruction by tumor)
- A biliary stent ≥ 9F or biliary bypass is required before treatment if there is biliary obstruction by tumor
- Urine protein:creatinine ratio ≤ 1.0
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No significant traumatic injury within the past 28 days
- No serious non-healing wounds, ulcers, or bone fractures
- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
- No myocardial infarction, unstable angina, or cerebrovascular accident within the past 6 months
- No NYHA class II-IV congestive heart failure
- Class II defined as symptoms of fatigue, dyspnea or other symptoms with ordinary physical activity
- No clinically significant peripheral vascular disease
- Pre-existing hypertension allowed, provided that the patient is receiving a stable antihypertensive regimen and has a blood pressure ≤ 150/100 mm Hg at the time of enrollment
- Must have adequate oral intake of > 1500 calories/day and be able to maintain hydration OR have access for supplemental enteral feeding (nasoenteral tube, feeding jejunostomy, or percutaneous endoscopic gastrostomy tube)
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy or radiotherapy for pancreatic cancer
- More than 28 days since prior and no anticipated need for concurrent major surgical procedures
- More than 7 days since prior minor surgical procedures such as laparoscopy, fine needle aspirations, or core biopsies
- No treatment plan requiring treatment of > 50% of the liver at a dose > 30 Gy or > 50% of the total kidney volume at a dose > 18 Gy
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent investigational agents
- No oral or parenteral anticoagulation unless patients is receiving a stable dose of anticoagulant
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104-4283
About this study
Official title: A Phase II Study of Gemcitabine, Oxaliplatin and Bevacizumab Followed by 5-Fluorouracil, Oxaliplatin, Bevacizumab and Radiotherapy in Patients With Locally Advanced Pancreatic Cancer
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as gemcitabine, oxaliplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving bevacizumab together with combination chemotherapy and radiation therapy may kill more tumor cells.
PURPOSE: The phase II trial is studying the side effects and how well giving bevacizumab together with gemcitabine, oxaliplatin, fluorouracil, and radiation therapy works in treating patients undergoing surgery for locally advanced pancreatic cancer.
Read the detailed description
OBJECTIVES:
Primary
- To describe the toxicity of bevacizumab with gemcitabine and oxaliplatin, when therapy is given before chemoradiotherapy, in patients with locally advanced pancreatic cancer.
- To describe the toxicity of bevacizumab with oxaliplatin, fluorouracil, and concomitant radiotherapy in these patients.
- To define progression-free survival, time to progression, and overall survival of patients treated with this regimen.
Second
- To determine the percentage of potentially resectable patients who are ultimately able to proceed to successful resection.
- To determine the relationship between markers of apoptosis in tumor cells (including MIF, CREB, HIF-1-alpha expression/polymorphism, and others) and response to therapy.
- To define response rates in patients treated with this regimen.
OUTLINE:
- Neoadjuvant therapy: Patients receive gemcitabine IV over 100 minutes and bevacizumab IV over 30-90 minutes on day 1 and oxaliplatin IV over 2 hours on day 2. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Between 4-6 weeks after completion of initial therapy, patients undergo radiotherapy once daily, 5 days a week, for 5-6 weeks. Beginning within 48 hours after initiation of radiotherapy, patients receive fluorouracil IV continuously through completion of radiotherapy. Patients also receive concurrent oxaliplatin IV over 2 hours on days 1, 15 and 29 and bevacizumab IV on days 1 and 15.
- Surgery: Four to six weeks after completion of neoadjuvant therapy, patients undergo resection of the tumor. Patients with no evidence of disease progression and who undergo successful surgical intervention (i.e., R0 resection) proceed to adjuvant chemotherapy within the next 6-10 weeks.
- Adjuvant therapy: Patients receive gemcitabine and bevacizumab for 4 courses as in neoadjuvant therapy.
Patients undergo collection of tumor tissue samples at the time of diagnosis, prior to treatment by endoscopic ultrasound or laparoscopy, or during surgical resection following neoadjuvant therapy. Paraffin-embedded tumor tissue specimens obtained at baseline are analyzed by immunohistochemistry to assess tumor vascularity and angiogenic activity. Tumor vascularity is assessed via immunostaining of tumor specimens with the pan-endothelial cell marker, anti-CD34, for evaluation of tumor blood vessels. Angiogenic activity is assessed by analyzing pERK1/2, Ki67, and the pericyte coverage index in tumor specimens. Patients also undergo blood collection to determine plasma levels of VEGF at 4 weeks prior to initial chemotherapy and bevacizumab, at up to 48 hours prior to chemoradiotherapy and bevacizumab, and at up to 48 hours prior to adjuvant chemotherapy and bevacizumab.
After completion of study therapy, patients are followed every 2 months for the first year, and then every 3 months thereafter.
- Conditions
- Pancreatic Cancer
- Being tested
- bevacizumab, fluorouracil, gemcitabine hydrochloride, oxaliplatin, immunohistochemistry staining method
- Keywords
- stage IV pancreatic cancer, recurrent pancreatic cancer
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumabBiological
fluorouracilDrug
oxaliplatinDrug
laboratory biomarker analysisOther
conventional surgeryProcedure or surgery
endoscopic biopsyProcedure or surgery
laparoscopyProcedure or surgery
radiation therapyRadiation
| Study group | Role | What they receive |
|---|---|---|
| GemOx and Bev, then chemoradiation, then surgery | Experimental | Gemcitabine 1000 mg/m2 over 100 min on day 1 every 2 weeks
Oxaliplatin 85 mg/m2 over 2 hours on day 2 every 2 weeks
Bevacizumab 10 mg/kg over 90 minutes on day 1 every 2 weeks. Infusion duration may be shortened in subsequent courses if tolerated.
One cycle is 2 weeks. Chemoradiation to begin prior to 4 weeks from last dose of Gem. Between 4 and 6 weeks following chemoradiotherapy, patients will undergo re-staging with CT or MRI and CA 19-9. If there is no evidence of disease progression, the patient will be referred to the surgeon for re-evaluation and consideration of surgical intervention Receives: Biological: bevacizumab; Drug: fluorouracil; Drug: gemcitabine hydrochloride; Drug: oxaliplatin; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Procedure: conventional surgery; Procedure: endoscopic biopsy; Procedure: laparoscopy; Radiation: radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate pre-radiation chemotherapy and bevacizumab and after 5-6 weeks of concurrent chemoradiotherapy and bevacizumab
Response rate pre-radiation chemotherapy and bevacizumab and after 5-6 weeks of concurrent chemoradiotherapy and bevacizumab
Measured: after 6-12 weeks
Progression-free survival
to be assessed after completion of treatment
Measured: approximately 26 weeks
Secondary outcomes (1)
Percentage of potentially resectable patients who are able to proceed to successful resection
after chemoradiation, those who can proceed to surgery
Measured: approximately 12 weeks from initial chemo start
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2008 (estimated)
- Study startMar 2007
- Primary completionSep 2011
- Study completionSep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Peter O'Dwyer, MD, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00602602
- Sponsor's protocol ID
- CDR0000580812
- Other IDs
- UPCC-04206, GENENTECH-UPCC-04206, UPCC-805957
- Status last verified
- Apr 2020
- First submitted
- 22 Jan 2008
- Last updated
- 27 Apr 2020
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Gemcitabine, Oxaliplatin and Bevacizumab Followed by 5-Fluorouracil, Oxaliplatin, Bevacizumab and Radiotherapy in Patients With Locally Advanced Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT00602602
- Acronym / sponsor ID
- CDR0000580812
- Conditions
- Pancreatic Cancer
- Keywords
- stage IV pancreatic cancer, recurrent pancreatic cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Mar 2007
- Primary completion
- Sep 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 28 Jan 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as gemcitabine, oxaliplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving bevacizumab together with combination chemotherapy and radiation therapy may kill more tumor cells.
PURPOSE: The phase II trial is studying the side effects and how well giving bevacizumab together with gemcitabine, oxaliplatin, fluorouracil, and radiation therapy works in treating patients undergoing surgery for locally advanced pancreatic cancer.
Detailed description
OBJECTIVES:
Primary
- To describe the toxicity of bevacizumab with gemcitabine and oxaliplatin, when therapy is given before chemoradiotherapy, in patients with locally advanced pancreatic cancer.
- To describe the toxicity of bevacizumab with oxaliplatin, fluorouracil, and concomitant radiotherapy in these patients.
- To define progression-free survival, time to progression, and overall survival of patients treated with this regimen.
Second
- To determine the percentage of potentially resectable patients who are ultimately able to proceed to successful resection.
- To determine the relationship between markers of apoptosis in tumor cells (including MIF, CREB, HIF-1-alpha expression/polymorphism, and others) and response to therapy.
- To define response rates in patients treated with this regimen.
OUTLINE:
- Neoadjuvant therapy: Patients receive gemcitabine IV over 100 minutes and bevacizumab IV over 30-90 minutes on day 1 and oxaliplatin IV over 2 hours on day 2. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Between 4-6 weeks after completion of initial therapy, patients undergo radiotherapy once daily, 5 days a week, for 5-6 weeks. Beginning within 48 hours after initiation of radiotherapy, patients receive fluorouracil IV continuously through completion of radiotherapy. Patients also receive concurrent oxaliplatin IV over 2 hours on days 1, 15 and 29 and bevacizumab IV on days 1 and 15.
- Surgery: Four to six weeks after completion of neoadjuvant therapy, patients undergo resection of the tumor. Patients with no evidence of disease progression and who undergo successful surgical intervention (i.e., R0 resection) proceed to adjuvant chemotherapy within the next 6-10 weeks.
- Adjuvant therapy: Patients receive gemcitabine and bevacizumab for 4 courses as in neoadjuvant therapy.
Patients undergo collection of tumor tissue samples at the time of diagnosis, prior to treatment by endoscopic ultrasound or laparoscopy, or during surgical resection following neoadjuvant therapy. Paraffin-embedded tumor tissue specimens obtained at baseline are analyzed by immunohistochemistry to assess tumor vascularity and angiogenic activity. Tumor vascularity is assessed via immunostaining of tumor specimens with the pan-endothelial cell marker, anti-CD34, for evaluation of tumor blood vessels. Angiogenic activity is assessed by analyzing pERK1/2, Ki67, and the pericyte coverage index in tumor specimens. Patients also undergo blood collection to determine plasma levels of VEGF at 4 weeks prior to initial chemotherapy and bevacizumab, at up to 48 hours prior to chemoradiotherapy and bevacizumab, and at up to 48 hours prior to adjuvant chemotherapy and bevacizumab.
After completion of study therapy, patients are followed every 2 months for the first year, and then every 3 months thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GemOx and Bev, then chemoradiation, then surgery | Experimental | Biological: bevacizumab, Drug: fluorouracil, Drug: gemcitabine hydrochloride, Drug: oxaliplatin, Other: immunohistochemistry staining method, Other: laboratory biomarker analysis, Procedure: conventional surgery, Procedure: endoscopic biopsy, Procedure: laparoscopy, Radiation: radiation therapyGemcitabine 1000 mg/m2 over 100 min on day 1 every 2 weeks Oxaliplatin 85 mg/m2 over 2 hours on day 2 every 2 weeks Bevacizumab 10 mg/kg over 90 minutes on day 1 every 2 weeks. Infusion duration may be shortened in subsequent courses if tolerated. One cycle is 2 weeks. Chemoradiation to begin prior to 4 weeks from last dose of Gem. Between 4 and 6 weeks following chemoradiotherapy, patients will undergo re-staging with CT or MRI and CA 19-9. If there is no evidence of disease progression, the patient will be referred to the surgeon for re-evaluation and consideration of surgical intervention |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bevacizumab | Biological | GemOx and Bev, then chemoradiation, then surgery |
| fluorouracil | Drug | GemOx and Bev, then chemoradiation, then surgery |
| gemcitabine hydrochloride | Drug | GemOx and Bev, then chemoradiation, then surgery |
| oxaliplatin | Drug | GemOx and Bev, then chemoradiation, then surgery |
| immunohistochemistry staining method | Other | GemOx and Bev, then chemoradiation, then surgery |
| laboratory biomarker analysis | Other | GemOx and Bev, then chemoradiation, then surgery |
| conventional surgery | Procedure or surgery | GemOx and Bev, then chemoradiation, then surgery |
| endoscopic biopsy | Procedure or surgery | GemOx and Bev, then chemoradiation, then surgery |
| laparoscopy | Procedure or surgery | GemOx and Bev, then chemoradiation, then surgery |
| radiation therapy | Radiation | GemOx and Bev, then chemoradiation, then surgery |
Primary outcome
Response rate pre-radiation chemotherapy and bevacizumab and after 5-6 weeks of concurrent chemoradiotherapy and bevacizumab
Time frame: after 6-12 weeks
Response rate pre-radiation chemotherapy and bevacizumab and after 5-6 weeks of concurrent chemoradiotherapy and bevacizumab
Progression-free survival
Time frame: approximately 26 weeks
to be assessed after completion of treatment
1 secondary outcome
Percentage of potentially resectable patients who are able to proceed to successful resection
Time frame: approximately 12 weeks from initial chemo start
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter O'Dwyer, MD principal investigator
Abramson Cancer Center at Penn Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing bevacizumab, fluorouracil and gemcitabine hydrochloride in people with Pancreatic Cancer, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response rate pre-radiation chemotherapy and bevacizumab and after 5-6 weeks of concurrent chemoradiotherapy and bevacizumab (time frame: after 6-12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2020.