Stereotactic Body Radiation + Chemotherapy for Pancreatic Cancer
Recruiting in Palo Alto (17 mi)
Overseen byChi Lin, MD, PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Chi Lin, MD, PhD
Must not be taking: Zometa
Disqualifiers: Pregnancy, HIV, Cardiac arrhythmia, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This randomized phase II trial will study how well hypofractionated stereotactic body radiation therapy and fluorouracil or capecitabine with or without zoledronic acid work in treating patients with pancreatic cancer that has spread to nearby tissue or lymph nodes. Hypofractionated stereotactic body radiation therapy is a specialized radiation therapy that sends higher doses of x-rays over a shorter period of time directly to the tumor using smaller doses over several days which may cause less damage to normal tissue. Drugs used in chemotherapy, such as fluorouracil and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Zoledronic acid is used in cancer patients to reduce cancer symptoms and may make tumor cells more sensitive to radiation. Giving hypofractionated stereotactic body radiation therapy and fluorouracil or capecitabine with or without zoledronic acid may work better in treating patients with pancreatic cancer.
Do I need to stop my current medications for this trial?
The trial protocol does not specify whether you need to stop taking your current medications. However, if you are currently taking Zometa, you must stop at least 3 weeks before starting the trial treatment.
What data supports the effectiveness of the treatment Stereotactic Body Radiation + Chemotherapy for Pancreatic Cancer?
Research indicates that combining fluorouracil (5-FU) with radiation therapy can improve outcomes in gastrointestinal cancers, including pancreatic cancer. Capecitabine, an oral form of 5-FU, has shown promise in enhancing the effects of radiation therapy, potentially leading to better tumor control and increased survival.
12345Is the combination of Stereotactic Body Radiation and Chemotherapy safe for humans?
Capecitabine (Xeloda) and 5-fluorouracil (5-FU) have been used in various cancer treatments, including colorectal and breast cancer, with generally manageable side effects. Studies have shown that these drugs, when used with radiation therapy, are well tolerated, although the specific safety of the combination with Stereotactic Body Radiation Therapy for pancreatic cancer is not detailed in the available research.
678910How is the treatment of Stereotactic Body Radiation + Chemotherapy for Pancreatic Cancer different from other treatments?
This treatment combines stereotactic body radiation therapy (SBRT), which delivers high doses of radiation precisely to the tumor, with chemotherapy drugs like Capecitabine and Fluorouracil. This approach aims to improve local control and survival rates by targeting the tumor more effectively while sparing surrounding healthy tissue, which is different from traditional chemotherapy or radiation methods that may affect more of the surrounding area.
1112131415Eligibility Criteria
This trial is for adults with locally advanced pancreatic cancer that hasn't spread far. They should have assessable disease, no recent chemo for other cancers, and their major organs must function well. It's not for those with allergies to Zometa, serious heart issues, pregnant or nursing women, certain prior cancers unless cured over 5 years ago, active severe gastrointestinal problems, HIV infection or liver insufficiency.Inclusion Criteria
Your platelet count is 100,000/uL or more.
You need to have a certain level of white blood cells called neutrophils in your body.
I had radiation for cancer other than pancreatic over 5 years ago, with no overlap or current cancer.
+9 more
Exclusion Criteria
I am not allergic to Zometa or anti-nausea medications used in this treatment.
I have no active stomach ulcers, bleeding, serious bowel issues, or history of bowel surgery.
I have HIV or liver problems.
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Pre-Treatment
Patients receive zoledronic acid IV over no less than 15 minutes 1 week prior to radiation therapy
1 week
Radiation and Chemotherapy
Patients undergo hypofractionated stereotactic body radiation therapy in 5 fractions on days 1-5 and receive fluorouracil IV or capecitabine PO for 4 weeks
4 weeks
Surgery
Patients undergo surgery 6-8 weeks after completion of radiation therapy
6-8 weeks post-radiation
Follow-up
Participants are monitored for safety and effectiveness after treatment
30 days, then every 3 months for the first year, every 4 months for the second year, and every 6 months thereafter
Participant Groups
The study tests if high-dose radiation given in a short time (stereotactic body radiation) combined with chemotherapy drugs fluorouracil or capecitabine improves outcomes. Some patients will also receive zoledronic acid to see if it enhances treatment by making cancer cells more sensitive to radiation.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm B (zoledronic acid, chemotherapy, radiation therapy)Experimental Treatment6 Interventions
Patients receive zoledronic acid IV over no less than 15 minutes 1 week prior to radiation therapy. Patients undergo hypofractionated stereotactic body radiation therapy and receive treatment with fluorouracil IV or capecitabine PO as in Arm A. Patients then undergo surgery 6-8 weeks after completion of radiation therapy.
Group II: Arm A (chemotherapy, radiation therapy)Active Control5 Interventions
Patients undergo hypofractionated stereotactic body radiation therapy in 5 fractions on days 1-5. Patients receive fluorouracil IV over 24 hours on day 1 weekly for 4 weeks or capecitabine PO every 12 hours starting the evening before day 1 of radiation therapy for 4 weeks as per standard of care. Patients then undergo surgery 6-8 weeks after completion of radiation therapy.
Capecitabine is already approved in European Union, United States, Canada, Japan for the following indications:
🇪🇺 Approved in European Union as Xeloda for:
- Colorectal cancer
- Breast cancer
🇺🇸 Approved in United States as Xeloda for:
- Colorectal cancer
- Breast cancer
🇨🇦 Approved in Canada as Xeloda for:
- Colorectal cancer
- Breast cancer
🇯🇵 Approved in Japan as Xeloda for:
- Colorectal cancer
- Breast cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Nebraska Medical CenterOmaha, NE
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Who Is Running the Clinical Trial?
Chi Lin, MD, PhDLead Sponsor
University of NebraskaLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Capecitabine and radiation therapy for advanced gastrointestinal malignancies. [2015]Accumulating data indicate a beneficial effect of combining infusional fluorouracil (5-FU) with radiation therapy in gastrointestinal cancers, and phase II/III studies are under way to examine this approach in a variety of tumor types. The oral fluoropyrimidine capecitabine (Xeloda) provides a more convenient approach to radiosensitization. The agent has good single-agent activity in a variety of tumor types. The final step in activation of the drug to 5-FU occurs via activity of thymidine phosphorylase; thymidine phosphorylase activity is markedly upregulated in many tumor tissues compared with healthy tissue (Miwa M, Ura M, Nishida M, et al: Eur J Cancer 34:1274-1281, 1998), allowing greater accumulation of 5-FU in tumor tissue, and there is evidence indicating that radiation therapy results in augmented upregulation of this enzyme. A variety of data suggest benefits of 5-FU as a radiosensitizer in improving outcome of radiation therapy in a number of gastrointestinal cancers, including data indicating improved survival with this chemoradiation therapy approach. Prospective and randomized studies of 5-FU-based chemoradiation are under way in esophageal, gastric, biliary tract, pancreatic, rectal, and anal cancer. Early phase studies are planned to examine the combination of capecitabine, celecoxib (Celebrex), and radiation therapy in esophageal cancer and pancreatic cancer and to compare the effects of capecitabine and capecitabine/oxaliplatin (Eloxatin) with radiation therapy in rectal cancer. A phase III trial comparing capecitabine and infusional 5-FU in chemoradiation therapy in rectal cancer has also been planned. Additional studies should be conducted in gastric, biliary tract, and anal cancer. Capecitabine shows promise in replacing infusional 5-FU as the platform for gastrointestinal chemoradiation therapy.
Comparison of capecitabine and 5-fluorouracil in chemoradiotherapy for locally advanced pancreatic cancer. [2021]Although capecitabine has theoretical advantages in the pharmacokinetics, such as higher intratumoral and lower systemic concentration, relative to bolus 5-fluorouracil (5-FU), outcomes of chemoradiotherapy (CRT) with capecitabine or bolus 5-FU have not been directly compared in patients with locally advanced pancreatic cancer. Therefore, we retrospectively compared the outcomes, including toxicity, tumor response, and overall survival, of oral capecitabine plus radiotherapy (RT) with bolus 5-FU plus RT, in patients with locally advanced pancreatic cancer.
Pancreatic cancer: are we moving forward yet? Highlights from the Gastrointestinal Cancers Symposium. Orlando, FL, USA. January 20th, 2007. [2018]Survival for patients with pancreatic cancer remains abysmal. Standard treatment for resected and locally advanced disease usually consists of 5-fluorouracil (5-FU, either bolus or continuous infusion) and external beam radiation. However, recent studies have shown the role of gemcitabine either used alone or incorporated with 5-FU and external beam radiation in this setting. Gemcitabine and erlotinib (Tarceva) are currently the only standard chemotherapeutic agents approved by FDA for the treatment of advanced pancreatic cancer. Combination chemotherapy trials incorporating gemcitabine with other agents such as 5-FU, oxaliplatin, or capecitabine generally show improved outcomes in objective response rates but with little or no improvement in survival in phase III trials. In this article, the author summarizes the key studies in pancreatic cancer presented at the 2007 Gastrointestinal Cancers Symposium (Orlando, FL, USA; January, 2007). The studies discussed here include preliminary results of the Cancer and Leukemia Group B (CALGB) phase III trial of gemcitabine plus bevacizumab and activity of other targeted agents including sorafenib, cetuximab, retrospective and population-based studies evaluating the role of chemo-radiotherapy and radiotherapy, an analysis of 3,306 patients from the Surveillance, Epidemiology and End Results (SEER) database evaluating the predictive role of lymph nodes in survival following pancreatectomy and the assessment of novel agents, such as Genexol-PM and S-1.
Protracted 5-fluorouracil infusion with concurrent radiotherapy as a treatment for locally advanced pancreatic carcinoma. [2013]Radiotherapy plus bolus 5-fluorouracil (5-FU) is generally accepted as the standard treatment for locally advanced pancreatic carcinoma. To intensify the antitumor effect of chemotherapy, the authors administered protracted 5-FU infusion with concurrent radiotherapy. The aim of this study was to determine the feasibility and effectiveness of this combined therapy.
Chemoradiotherapy as preoperative treatment in locally advanced unresectable pancreatic cancer patients: results of a feasibility study. [2019]The combination of radiotherapy and fluorouracil (5-FU) in patients with locally unresectable pancreatic carcinoma has led to a significant increase in survival in comparison with radiotherapy alone. Doxifluridine (5-DFUR) is an orally active fluoropyrimidine, and its cytotoxic metabolite (5-FU) may concentrate in areas of high tumor vascularization. This trial was carried out with the aims of improving locoregional control and making lesions resectable in patients with unresectable pancreatic cancer.
Prospective phase I study of capecitabine and oxaliplatin concurrent with radiation therapy for the treatment of locally advanced pancreatic adenocarcinoma, and retrospective comparison to concurrent 5-fluorouracil/radiation and gemcitabine/radiation. [2022]The aims of this study is to determine the maximum tolerated dose of capecitabine and oxaliplatin (CAPOX) delivered concurrent with radiation therapy (RT) in the treatment of locally advanced pancreatic adenocarcinoma and to retrospectively compare outcomes with this regimen to concurrent 5-fluorouracil or capecitabine with RT (5FU-RT) or concurrent gemcitabine-based chemotherapy with RT (GEM-RT).
Fluoropyrimidines: a critical evaluation. [2017]After nearly four decades of clinical experience with the fluoropyrimidines, 5-fluorouracil (5-FU) remains an integral part of chemotherapy for colorectal cancer. A range of 5-FU treatment regimens with or without biochemical modulation are currently used and toxicity appears to be schedule dependent. The use of oral 5-FU was abandoned because of erratic absorption caused by varying levels of dihydropyrimidine dehydrogenase (DPD) found in the gastrointestinal tract. This effect may be overcome by administering agents that are converted to 5-FU or by inhibiting or inactivating DPD. Xeloda((R)) (capecitabine) was designed as an orally administered, selectively tumoractivated(TM) cytotoxic agent which achieves higher levels of 5-FU in the primary tumor than in plasma or other tissues. The United States Food and Drug Administration (FDA) has approved Xeloda for use in patients with metastatic breast cancer resistant to paclitaxel and in whom further anthracycline therapy is contraindicated. Xeloda is also registered in Canada, Switzerland, Thailand and Argentina. In phase II clinical trials in colorectal cancer, Xeloda produced response rates of 21-24% and median time to disease progression of 127-230 days. Other oral agents in development for the treatment of colorectal cancer include tegafur/uracil plus oral leucovorin, S-1 and eniluracil plus oral 5-FU.
Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. [2022]To compare the efficacy and safety of orally administered capecitabine (Xeloda; Roche Laboratories, Inc, Nutley, NJ), a novel fluoropyrimidine carbamate designed to mimic continuous fluorouracil (5-FU) infusion but with preferential activation at the tumor site, with that of intravenous (IV) 5-FU plus leucovorin (5-FU/LV) as first-line treatment for metastatic colorectal cancer.
Potential of Xeloda in colorectal cancer and other solid tumors. [2017]For over four decades, 5-fluorouracil (5-FU) has been the mainstay of therapy for colorectal cancer and a major cytotoxic agent for treating gastrointestinal tumors and a variety of others, including breast and head and neck cancers. Xeloda (capecitabine) is a new drug that is administered orally and has been rationally designed to generate 5-FU selectively within solid tumors. Theoretically, it has two major advantages, which should translate into an improved therapeutic index: firstly, enhanced drug concentration at the cancer site and therefore greater anti-tumor activity and secondly, reduced drug levels in non-tumor tissues, with a consequent reduction in systemic toxicity. After promising preclinical studies, phase I clinical trials of Xeloda have been performed with a variety of schedules, both with and without the oral biomodulator leucovorin. Anti-tumor activity has been observed with all regimens tested. In the setting of colorectal cancer, a randomized phase II study substantiated the phase I reports of activity and established the most promising regimen for phase III clinical trials. Patients in the phase II trial were randomly selected to receive either continuous Xeloda, intermittent Xeloda or intermittent Xeloda plus leucovorin. There were complete or partial responses in 21% of patients in the continuous arm, 24% in the intermittent arm, and 23% in the arm with intermittent Xeloda plus leucovorin. In addition, 51-63% of patients in each arm achieved stable disease. Therapy was well tolerated in all three arms. The intermittent regimen of Xeloda alone was associated with a longer time to disease progression and offered a one-week rest period to the patient. It was therefore selected for subsequent studies. Two randomized phase III trials of Xeloda versus the 'Mayo' regimen in patients with advanced colorectal cancer have completed recruitment. They are designed to demonstrate at least equivalent efficacy, with important secondary endpoints of comparisons of toxicity, medical care utilization, and quality of life. No formal results are yet available from these studies. The same regimen of Xeloda is now being evaluated in a large scale adjuvant study, which is expected to recruit approximately 1,700 Dukes' C colonic cancer patients (X-ACT study). The modest toxicity of Xeloda (particularly its low incidence of neutropenia) makes it a suitable candidate for novel combination therapies involving other agents that are active in colorectal cancer, including camptothecin and its analogues, oxaliplatin and radiotherapy. Further studies of Xeloda can be expected with other diseases known to be responsive to fluoropyrimidines, together with diseases traditionally thought to be resistant.
Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer. [2022]Capecitabine (Xeloda) is a new orally administered fluoropyrimidine carbamate that was rationally designed to exert its effect by tumor-selective activation. We attempted to evaluate the efficacy and toxicity of preoperative chemoradiation using capecitabine in locally advanced rectal cancer.
Stereotactic Body Radiation Therapy for Locally Advanced Pancreatic Cancer: A Systematic Review and Pooled Analysis of 19 Trials. [2023]Although surgery is the standard of care for resectable pancreatic cancer (PC), standard-dose chemoradiation therapy and chemotherapy alone are suitable for patients with unresectable disease. Stereotactic body radiation therapy (SBRT) is an alternative, focused local therapy that delivers high radiation doses within a few fractions to the cancer, sparing the surrounding critical tissue. We performed a systematic review and pooled analysis of published trials to evaluate the efficacy and safety of this emerging treatment modality.
Preoperative treatment with mFOLFIRINOX or Gemcitabine/Nab-paclitaxel +/- isotoxic high-dose stereotactic body Radiation Therapy (iHD-SBRT) for borderline resectable pancreatic adenocarcinoma (the STEREOPAC trial): study protocol for a randomised comparative multicenter phase II trial. [2023]For patients with pancreatic ductal adenocarcinoma (PDAC), surgical resection remains the only potentially curative treatment. Surgery is generally followed by postoperative chemotherapy associated with improved survival, yet neoadjuvant therapy is a rapidly emerging concept requiring to be explored and validated in terms of treatment options and oncological outcomes. In this context, stereotactic body radiation (SBRT) appears feasible and can be safely integrated into a neoadjuvant chemotherapy regimen of modified FOLFIRINOX (mFFX) with promising benefits in terms of R0 resection, local control and survival. However, the optimal therapeutic sequence is still not known, especially for borderline resectable PDAC, and the role of adding SBRT to chemotherapy in the neoadjuvant setting needs to be evaluated in randomised controlled trials. The aim of the STEREOPAC trial is to assess the impact and efficacy of adding isotoxic high-dose SBRT (iHD-SBRT) to neoadjuvant mFFX or Gemcitabine/Nab-Paclitaxel (Gem/Nab-P) in patients with borderline resectable PDAC.
Results of a prospective phase 2 clinical trial of induction gemcitabine/capecitabine followed by stereotactic ablative radiation therapy in borderline resectable or locally advanced pancreatic adenocarcinoma. [2023]Stereotactic ablative radiation therapy's (SABR's) great conformity and short duration has become an attractive treatment modality. We report a phase 2 clinical trial to evaluate efficacy and safety of induction chemotherapy (ICT) followed by SABR in patient with borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC).
Stereotactic body radiotherapy in pancreatic adenocarcinoma. [2023]Stereotactic body radiotherapy (SBRT) in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding tissue. This review aimed at the SBRT application in the treatment of pancreatic cancer.
Stereotactic body radiation therapy in pancreatic cancer: the new frontier. [2014]Pancreatic cancer (PCA) remains a disease with a poor prognosis. The majority of PCA patients are unable to undergo surgical resection, which is the only potentially curative option at this time. A combination of chemotherapy and chemoradiation (CRT) are standard options for patients with locally advanced, unresectable disease, however, local control and patient outcomes remains poor. Stereotactic body radiation therapy (SBRT) is an emerging treatment option for PCA. SBRT delivers potentially ablative doses to the pancreatic tumor plus a small margin over a short period of time. Early studies with single-fraction SBRT demonstrated excellent tumor control with high rates of toxicity. The implementation of SBRT (3-5 doses) has demonstrated promising outcomes with favorable tumor control and toxicity rates. Herein we discuss the evolving role of SBRT in PCA treatment.