Pancreatic CancerPhase 2NCT00089024
Combination Chemotherapy, and Radiation Therapy in Treating Patients With Locally Advanced Pancreatic Cancer
A Phase 2 study testing fluorouracil, gemcitabine hydrochloride and leucovorin calcium in people with Pancreatic Cancer, run by University of Nebraska at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving combination chemotherapy with radiation therapy before surgery may shrink the tumor so that it can be removed. Read more about this study
- Who is it for?
- Ages 19 to 120 years
- Conditions the study is for
- Pancreatic Cancer
- What is being tested?
- fluorouracil, gemcitabine hydrochloride and leucovorin calcium
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Feb 2004to 1 Dec 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 19 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of adenocarcinoma of the pancreas
- o Locally advanced disease
- Potentially resectable disease
- 19 years of age and over
- Karnofsky 60-100%
- Absolute granulocyte count ≥ 2,000/mm^3
Show all 11Show fewer
- Platelet count ≥ 100,000/mm^3
- Bilirubin ≤ 2.0 mg/dL (in the absence of biliary obstruction)
- If biliary obstruction is present, patients must undergo biliary decompression
- Bilirubin ≤ 3.0 mg/dL after biliary drainage has been established
- Creatinine ≤ 1.6 mg/dL
Who cannot join
- No early stage resectable disease
- No concurrent non-steroidal anti-inflammatory medication
- No evidence of distant metastases to the liver or peritoneal area according to imaging studies and laparoscopic staging
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No serious uncontrolled cardiac arrhythmia
Show all 15Show fewer
- Not pregnant or nursing
- No uncontrolled illness
- No active or ongoing infection requiring IV antibiotics
- No marked intolerance to 5-fluoropyrimidines (i.e., fluorouracil, floxuridine, capecitabine, or fluorocytosine)
- No allergy to sulfonamides, aspirin, or non-steroidal anti-inflammatory drugs
- No allergy to platinum compounds or to antiemetics appropriate for administration in conjunction with study chemotherapy
- No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or adequately treated noninvasive carcinoma
- No prior chemotherapy for pancreatic cancer
- No prior abdominal radiotherapy
Trial locations and contacts
1 site in 1 country.
United States1 site
Eppley Cancer Center, University of Nebraska Medical Center
Omaha, Nebraska, 68198-6805
About this study
Official title: A Phase II Study Of Neo-Adjuvant Chemotherapy And Radiation In Patients With Locally Advanced Pancreatic Cancer
RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving combination chemotherapy with radiation therapy before surgery may shrink the tumor so that it can be removed.
PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with radiation therapy works in treating patients who may undergo surgery for locally advanced pancreatic cancer.
Read the detailed description
OBJECTIVES:
- Determine the antitumor and clinical benefit response to neoadjuvant chemoradiotherapy comprising gemcitabine, fluorouracil, leucovorin calcium, and oxaliplatin in patients with potentially resectable locally advanced adenocarcinoma of the pancreas.
- Determine the toxic effects of this regimen in these patients.
- Determine the achieved steady-state plasma levels of gemcitabine and fluorouracil in these patients and correlate these plasma levels with clinical toxicity associated with this regimen.
- Determine the potential importance of polymorphic variations in genomic DNA of pertinent genes (whose protein products are targets of the antineoplastic drugs used in this study) on response to and toxicity of this regimen in these patients.
- Determine the gene expression profiles of primary and metastatic pancreatic tumors before and after treatment with this regimen.
OUTLINE:
- Neoadjuvant chemotherapy: Patients receive gemcitabine IV over 30 minutes and fluorouracil IV continuously over 24 hours on days 2 and 9, and leucovorin calcium orally on days 1 and 8 and IV on days 2 and 9. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
- Neoadjuvant chemoradiotherapy: Beginning on day 42, patients undergo chemoradiotherapy comprising oxaliplatin IV over 2 hours on days 42, 49, 56, 63, 70, and 77 and fluorouracil IV continuously on days 42-78 with external beam radiotherapy.
- Surgery: Patients undergo surgical resection 42-56 days after completion of chemoradiotherapy.
- Adjuvant chemotherapy: After post-operative recovery, patients receive 2 additional courses of gemcitabine, fluorouracil, and leucovorin calcium. If surgical resection is not possible, patients with stable or responsive disease resume gemcitabine, fluorouracil, and leucovorin calcium indefinitely in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
- Conditions
- Pancreatic Cancer
- Being tested
- fluorouracil, gemcitabine hydrochloride, leucovorin calcium, oxaliplatin, adjuvant therapy
- Keywords
- adenocarcinoma of the pancreas, stage II pancreatic cancer, stage III 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.
fluorouracilDrug
Also called Tolak, Fluoroplex, Carac
2700 mg/m5 IV over 24 hr after gemcitabine weeks 1 \& 2; Repeat one 3-week cycle starting day 22
Also called Gemzar
750 (females) or 900 (males) mg/m5 IV over 30 min (day 2)weeks 1 \& 2; Repeat one 3-week cycle starting day 22
Also called folic acid analog
20 mg/m5 PO (day 1) and 20 mg/m5 IV (day 2) weeks 1 and 2; Repeat one 3-week cycle starting day 22
oxaliplatinDrug
Also called chemotherapy
48 mg/m5 IV over 2 hr weeks 1, 2, 4, and 5
adjuvant therapyProcedure or surgery
Patients who have undergone surgical resection, after post-operative recovery, will receive two additional cycles of gemcitabine/5-FU/leucovorin. Patients will then be followed at 3 month intervals with a history and physical exam, CT scan of the chest/abdomen/pelvis, and tumor markers.
If surgical resection is not possible, patients with stable or responsive disease will resume gemcitabine/5-FU/leucovorin and continue on it indefinitely until disease progression provided the patient tolerates it and wishes to remain on therapy.
conventional surgeryProcedure or surgery
Restaging with repeat imaging studies will be performed four weeks after completion of the chemo-radiation. If no contraindication for surgical resection is identified, resection will be performed six to eight weeks after completing chemoradiation. At the time of surgical resection, an extensive examination of the abdomen will be performed to exclude the presence of metastatic disease. All operations will be performed with curative intent with resection of all gross tumor (ie R0 [negative margins] or R1 [positive microscopic margins]). Resection of adjacent involved organs or vascular structures will be performed as clinically indicated.
neoadjuvant therapyProcedure or surgery
Eligible patients will receive an initial two cycles of chemotherapy with gemcitabine 750 (females) or 900 (males) mg/m5 over 30 minutes followed by a 24-hour infusion of fluorouracil 2700 mg/m5 on days 2 and 9 of a 21-day cycle . Calcium leucovorin 20 mg/m5 will be given orally on days 1 and 8 and by IV push on days 2 and 9 prior to the 5-FU. A window of -2 up to +7 days will be allowed to start planned cycles of therapy provided all other criteria to restart the new cycle has been met. Patients will require a central venous catheter (Port, Hickman or Groshong catheter) for the administration of 5-FU.
radiation therapyRadiation
A re-staging CT scan, which will be obtained as part of the radiation simulation, will be used to assess any possible response to the initial two cycles of chemotherapy. Unless the patient has developed evidence of metastatic disease, chemoradiation will proceed. Patients who required no treatment delays will commence chemoradiation on day 42. If a one-week delay is needed before cycle 2 of neo-adjuvant chemotherapy can be delivered, the patient will begin chemoradiation on day 49 provided treatment-related toxicity has resolved. If cycle 2 could not be given (2 or more week delay for resolution of treatment-related toxicity), then chemoradiation will begin once toxicity has resolved (may be earlier than day 42).
| Study group | Role | What they receive |
|---|---|---|
| treatment | Experimental | see interventions Receives: Drug: fluorouracil; Drug: gemcitabine hydrochloride; Drug: leucovorin calcium; Drug: oxaliplatin; Procedure: adjuvant therapy; Procedure: conventional surgery; Procedure: neoadjuvant therapy; Radiation: radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Surgical Exploration
Patients who completed chemotherapy \& chemo-radiation had restaging imaging studies 4 weeks after completion of chemo-radiation. If there were no contraindications for surgical resection, surgical exploration was performed 6-8 weeks after completing chemo-radiation
Measured: After 6 weeks of chemotherapy and then after 4 weeks of chemo-radiation.
Number of Participants Experiencing Grade 3-4 Toxicity While Receiving the Study Treatment
Toxicity event collected during Induction chemotherapy (CT) - two 3-week cycles, Concurrent CT and Radiation Therapy (CRT) (approximately 5.5 weeks), post CRT (4 weeks after the end of CRT), 2-3 months post CRT (8-12 weeks after the end of CRT)
Measured: From time of first dose until 30 days following final treatment, approximately 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2004 (estimated)
- Study start25 Feb 2004
- Primary completion22 Jan 2010
- Study completion1 Dec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe 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
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jean L Grem, MD, Study chair, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00089024
- Sponsor's protocol ID
- 0035-04-FB
- Other IDs
- P30CA036727
- Status last verified
- Sep 2023
- First submitted
- 4 Aug 2004
- Last updated
- 29 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study Of Neo-Adjuvant Chemotherapy And Radiation In Patients With Locally Advanced Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT00089024
- Acronym / sponsor ID
- 0035-04-FB
- Conditions
- Pancreatic Cancer
- Keywords
- adenocarcinoma of the pancreas, stage II pancreatic cancer, stage III pancreatic cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 25 Feb 2004 (actual)
- Primary completion
- 22 Jan 2010 (actual)
- Study completion
- 1 Dec 2014 (actual)
- First posted
- 5 Aug 2004 (estimated)
- Results
- Posted 21 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving combination chemotherapy with radiation therapy before surgery may shrink the tumor so that it can be removed.
PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with radiation therapy works in treating patients who may undergo surgery for locally advanced pancreatic cancer.
Detailed description
OBJECTIVES:
- Determine the antitumor and clinical benefit response to neoadjuvant chemoradiotherapy comprising gemcitabine, fluorouracil, leucovorin calcium, and oxaliplatin in patients with potentially resectable locally advanced adenocarcinoma of the pancreas.
- Determine the toxic effects of this regimen in these patients.
- Determine the achieved steady-state plasma levels of gemcitabine and fluorouracil in these patients and correlate these plasma levels with clinical toxicity associated with this regimen.
- Determine the potential importance of polymorphic variations in genomic DNA of pertinent genes (whose protein products are targets of the antineoplastic drugs used in this study) on response to and toxicity of this regimen in these patients.
- Determine the gene expression profiles of primary and metastatic pancreatic tumors before and after treatment with this regimen.
OUTLINE:
- Neoadjuvant chemotherapy: Patients receive gemcitabine IV over 30 minutes and fluorouracil IV continuously over 24 hours on days 2 and 9, and leucovorin calcium orally on days 1 and 8 and IV on days 2 and 9. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
- Neoadjuvant chemoradiotherapy: Beginning on day 42, patients undergo chemoradiotherapy comprising oxaliplatin IV over 2 hours on days 42, 49, 56, 63, 70, and 77 and fluorouracil IV continuously on days 42-78 with external beam radiotherapy.
- Surgery: Patients undergo surgical resection 42-56 days after completion of chemoradiotherapy.
- Adjuvant chemotherapy: After post-operative recovery, patients receive 2 additional courses of gemcitabine, fluorouracil, and leucovorin calcium. If surgical resection is not possible, patients with stable or responsive disease resume gemcitabine, fluorouracil, and leucovorin calcium indefinitely in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| treatment | Experimental | Drug: fluorouracil, Drug: gemcitabine hydrochloride, Drug: leucovorin calcium, Drug: oxaliplatin, Procedure: adjuvant therapy, Procedure: conventional surgery, Procedure: neoadjuvant therapy, Radiation: radiation therapysee interventions |
Who may qualify
- Ages
- 19 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Diagnosis of adenocarcinoma of the pancreas
- o Locally advanced disease
- Potentially resectable disease
- 19 years of age and over
- Karnofsky 60-100%
Key exclusion criteria (15 listed)
- No early stage resectable disease
- No concurrent non-steroidal anti-inflammatory medication
- No evidence of distant metastases to the liver or peritoneal area according to imaging studies and laparoscopic staging
- No symptomatic congestive heart failure
- No unstable angina pectoris
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 |
|---|---|---|
| fluorouracilAlso: Tolak, Fluoroplex, Carac2700 mg/m5 IV over 24 hr after gemcitabine weeks 1 \& 2; Repeat one 3-week cycle starting day 22 | Drug | treatment |
| gemcitabine hydrochlorideAlso: Gemzar750 (females) or 900 (males) mg/m5 IV over 30 min (day 2)weeks 1 \& 2; Repeat one 3-week cycle starting day 22 | Drug | treatment |
| leucovorin calciumAlso: folic acid analog20 mg/m5 PO (day 1) and 20 mg/m5 IV (day 2) weeks 1 and 2; Repeat one 3-week cycle starting day 22 | Drug | treatment |
| oxaliplatinAlso: chemotherapy48 mg/m5 IV over 2 hr weeks 1, 2, 4, and 5 | Drug | treatment |
| adjuvant therapyPatients who have undergone surgical resection, after post-operative recovery, will receive two additional cycles of gemcitabine/5-FU/leucovorin. Patients will then be followed at 3 month intervals with a history and physical exam, CT scan of the chest/abdomen/pelvis, and tumor markers. If surgical resection is not possible, patients with stable or responsive disease will resume gemcitabine/5-FU/leucovorin and continue on it indefinitely until disease progression provided the patient tolerates it and wishes to remain on therapy. | Procedure or surgery | treatment |
| conventional surgeryRestaging with repeat imaging studies will be performed four weeks after completion of the chemo-radiation. If no contraindication for surgical resection is identified, resection will be performed six to eight weeks after completing chemoradiation. At the time of surgical resection, an extensive examination of the abdomen will be performed to exclude the presence of metastatic disease. All operations will be performed with curative intent with resection of all gross tumor (ie R0 [negative margins] or R1 [positive microscopic margins]). Resection of adjacent involved organs or vascular structures will be performed as clinically indicated. | Procedure or surgery | treatment |
| neoadjuvant therapyEligible patients will receive an initial two cycles of chemotherapy with gemcitabine 750 (females) or 900 (males) mg/m5 over 30 minutes followed by a 24-hour infusion of fluorouracil 2700 mg/m5 on days 2 and 9 of a 21-day cycle . Calcium leucovorin 20 mg/m5 will be given orally on days 1 and 8 and by IV push on days 2 and 9 prior to the 5-FU. A window of -2 up to +7 days will be allowed to start planned cycles of therapy provided all other criteria to restart the new cycle has been met. Patients will require a central venous catheter (Port, Hickman or Groshong catheter) for the administration of 5-FU. | Procedure or surgery | treatment |
| radiation therapyA re-staging CT scan, which will be obtained as part of the radiation simulation, will be used to assess any possible response to the initial two cycles of chemotherapy. Unless the patient has developed evidence of metastatic disease, chemoradiation will proceed. Patients who required no treatment delays will commence chemoradiation on day 42. If a one-week delay is needed before cycle 2 of neo-adjuvant chemotherapy can be delivered, the patient will begin chemoradiation on day 49 provided treatment-related toxicity has resolved. If cycle 2 could not be given (2 or more week delay for resolution of treatment-related toxicity), then chemoradiation will begin once toxicity has resolved (may be earlier than day 42). | Radiation | treatment |
Primary outcome
Surgical Exploration
Time frame: After 6 weeks of chemotherapy and then after 4 weeks of chemo-radiation.
Patients who completed chemotherapy \& chemo-radiation had restaging imaging studies 4 weeks after completion of chemo-radiation. If there were no contraindications for surgical resection, surgical exploration was performed 6-8 weeks after completing chemo-radiation
Number of Participants Experiencing Grade 3-4 Toxicity While Receiving the Study Treatment
Time frame: From time of first dose until 30 days following final treatment, approximately 24 weeks
Toxicity event collected during Induction chemotherapy (CT) - two 3-week cycles, Concurrent CT and Radiation Therapy (CRT) (approximately 5.5 weeks), post CRT (4 weeks after the end of CRT), 2-3 months post CRT (8-12 weeks after the end of CRT)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Pancreatic Cancer
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
RecruitingPhase 2/3
Multicenter Validation Trial of [18F]AlF-FAPI-74 for PET Imaging of Cancer-associated Fibroblasts Through Fibroblast Activation Protein Inhibitors (FAPI) in Different Tumor Types
Oesophageal Cancer, Gastric Cancer
RecruitingPhase 1
Modified FOLFIRINOX and Pentamidine in Advanced and Metastatic Pancreatic Cancer
Pancreatic Ductal Adenocarcinoma (PDAC)
RecruitingPhase 3
Atebimetinib + GnP as a First Line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma
Pancreatic Cancer, Pancreatic Cancer Metastatic
RecruitingPhase 3
Lanreotide Versus Placebo Before Surgery to Prevent a Surgical Complication Called a Pancreatic Fistula
Pancreatic Carcinoma, Pancreatic Neoplasm
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.
Jean L Grem, MD study chair
University of Nebraska
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 fluorouracil, gemcitabine hydrochloride and leucovorin calcium in people with Pancreatic Cancer, run by University of Nebraska 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?
The sponsor lists 11 inclusion and 15 exclusion criteria. 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 29 Sep 2023. 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?
Yes. Results are posted in the registry (first posted 21 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Surgical Exploration (time frame: After 6 weeks of chemotherapy and then after 4 weeks of chemo-radiation.). 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 29 Sep 2023.