Stereotactic Body Radiation + Chemotherapy for Pancreatic Cancer

Overseen By Chi Lin, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Chi Lin, MD, PhD

Must not be taking: Zometa

Disqualifiers: Pregnancy, HIV, Cardiac arrhythmia, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

46 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Pancreatic cancer, most commonly adenocarcinoma, is the fourth leading cause of cancer death in the United States. The mainstay of management centers on surgical resection (if resectable) and although low (15% to 20%), resectability rates are associated with dismal survival. An estimated 80% to 85% of the patients recur after surgical resection, leading to a median survival of 20 to 24 months and potentially even less depending on lymph nodal involvement or positive margins. The rationale for utilizing neoadjuvant therapy, commonly fluoropyrimidine-based or gemcitabine based chemotherapy or Chemoradiotherapy (CRT), involves possibly down staging borderline resectable and unresectable patients, potentially making them resectable candidates. This randomized phase II trial will study how well hypofractionated stereotactic body radiation therapy (SBRT) and fluorouracil or capecitabine with or without zoledronic acid work in treating participants 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 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.

Is 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. ^{1 2 3 4 5}

How 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. ^{6 7 8 9 10}

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. ^{11 12 13 14 15}

Who Is on the Research Team?

Chi Lin, MD, PhD

Principal Investigator

University of Nebraska

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Fluorouracil
• Stereotactic Body Radiation Therapy
• Zoledronic Acid

Trial Overview 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.

How Is the Trial Designed?

Group I: Arm B (zoledronic acid, chemotherapy, radiation therapy) Experimental Treatment 6 Interventions

Participants receive zoledronic acid IV over a minimum of 15 minutes 1 week prior to radiation therapy. Participants undergo hypofractionated stereotactic body radiation therapy and receive treatment with fluorouracil IV or capecitabine by mouth as in Arm A. Participants then undergo surgery 6-8 weeks after completion of radiation therapy.

Group II: Arm A (chemotherapy, radiation therapy) Active Control 5 Interventions

Participants undergo hypofractionated stereotactic body radiation therapy in 5 fractions on days 1-5. Participants receive fluorouracil IV over 24 hours on day 1 weekly for 4 weeks or capecitabine by mouth every 12 hours starting the evening before day 1 of radiation therapy for 4 weeks as per standard of care. Participants 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

Who Is Running the Clinical Trial?

Chi Lin, MD, PhD

Lead Sponsor

Trials

3

Recruited

190+

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Combining capecitabine (an oral fluoropyrimidine) with radiation therapy shows promise as a more convenient and effective approach for treating gastrointestinal cancers, with ongoing studies examining its efficacy compared to infusional fluorouracil (5-FU).

Capecitabine's activation to 5-FU is enhanced by thymidine phosphorylase, which is more active in tumor tissues, potentially leading to better drug accumulation in tumors and improved outcomes in radiation therapy, as indicated by ongoing and planned clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine and radiation therapy for advanced gastrointestinal malignancies. Rich, T.[2015]

In a study of 98 patients with locally advanced pancreatic cancer, capecitabine combined with radiotherapy resulted in significantly lower rates of severe toxicities compared to bolus 5-FU, indicating a safer treatment option.

Both treatment regimens showed similar effectiveness in terms of tumor response rates and overall survival, suggesting that capecitabine is a feasible alternative to 5-FU in chemoradiotherapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of capecitabine and 5-fluorouracil in chemoradiotherapy for locally advanced pancreatic cancer. Kim, YJ., Lee, WJ., Woo, SM., et al.[2021]

Recent studies indicate that gemcitabine, either alone or in combination with 5-fluorouracil and radiation, plays a significant role in the treatment of resected and locally advanced pancreatic cancer, although survival rates remain low.

Combination therapies involving gemcitabine with other agents like oxaliplatin or capecitabine have shown improved response rates in clinical trials, but they have not significantly enhanced overall survival according to phase III trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic cancer: are we moving forward yet? Highlights from the Gastrointestinal Cancers Symposium. Orlando, FL, USA. January 20th, 2007. Saif, MW.[2018]

In a Phase II trial involving 20 patients with locally advanced pancreatic carcinoma, the combination of protracted 5-fluorouracil infusion and concurrent radiotherapy demonstrated moderate effectiveness, with 10% of patients achieving a partial response and 80% maintaining stable disease.

The treatment was generally well-tolerated, with 85% of patients completing the therapy and only 20% experiencing severe toxicity, indicating that this approach could be a viable option for managing this challenging cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protracted 5-fluorouracil infusion with concurrent radiotherapy as a treatment for locally advanced pancreatic carcinoma. Ishii, H., Okada, S., Tokuuye, K., et al.[2013]

The combination of doxifluridine (5-DFUR) and radiotherapy improved the chances of surgical resection in patients with locally unresectable pancreatic cancer, achieving a 16% resectability rate in a study of 32 patients.

The median survival time for all patients was 9 months, with a 1-year survival rate of 31%, indicating that this treatment regimen is both feasible and potentially effective, with no severe toxic events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy as preoperative treatment in locally advanced unresectable pancreatic cancer patients: results of a feasibility study. Bajetta, E., Di Bartolomeo, M., Stani, SC., et al.[2019]

The study established that the maximum tolerated dose of capecitabine and oxaliplatin (CAPOX) combined with radiation therapy (RT) is safe for patients with locally advanced pancreatic adenocarcinoma, with acceptable toxicity observed at the highest dose level tested.

While CAPOX-RT showed a response rate of 38%, it did not improve overall survival compared to gemcitabine-based therapy (GEM-RT) or 5-fluorouracil (5FU-RT), indicating that while CAPOX-RT is tolerable, it may not be more effective than existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Hazard, L., Jones, K., Shaban, A., et al.[2022]

5-fluorouracil (5-FU) remains a key chemotherapy drug for colorectal cancer, but its oral form was previously abandoned due to inconsistent absorption; however, Xeloda (capecitabine) offers a solution by being an orally administered drug that is selectively activated in tumors, leading to higher local concentrations of 5-FU.

In phase II clinical trials for colorectal cancer, Xeloda demonstrated response rates of 21-24% and a median time to disease progression of 127-230 days, indicating its efficacy as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoropyrimidines: a critical evaluation. Brito, RA., Medgyesy, D., Zukowski, TH., et al.[2017]

Capecitabine, an oral medication, showed at least equivalent efficacy to intravenous 5-FU plus leucovorin in treating metastatic colorectal cancer, with an overall response rate of 18.9% compared to 15.0% for 5-FU/LV among 602 patients.

Capecitabine had a more favorable safety profile, resulting in significantly lower rates of stomatitis and neutropenia, while being associated with a higher incidence of hand-foot syndrome, making it a convenient and effective alternative to traditional IV treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. Van Cutsem, E., Twelves, C., Cassidy, J., et al.[2022]

Xeloda (capecitabine) is an oral medication designed to convert into 5-fluorouracil (5-FU) specifically within tumors, potentially increasing anti-tumor activity while reducing systemic toxicity, as shown in various phase I and II trials.

In a phase II trial for colorectal cancer, Xeloda demonstrated a response rate of 21-24% across different regimens, with good tolerability and a longer time to disease progression for the intermittent regimen, which was selected for further studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential of Xeloda in colorectal cancer and other solid tumors. Cassidy, J.[2017]

In a study of 45 patients with locally advanced rectal cancer, preoperative chemoradiation using capecitabine resulted in significant tumor downstaging, with 63% of primary tumors and 90% of lymph nodes showing downstaging, and a pathologic complete response in 31% of patients.

The treatment was found to be safe and well-tolerated, with no severe hematologic toxicities and manageable Grade 3 side effects, suggesting that capecitabine can effectively enhance surgical options, including sphincter-preserving surgeries for tumors near the anal verge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer. Kim, JS., Kim, JS., Cho, MJ., et al.[2022]

Stereotactic body radiation therapy (SBRT) shows promising efficacy for patients with locally advanced pancreatic cancer, with a pooled 1-year overall survival rate of 51.6% and a median overall survival of 17 months based on a systematic review of 19 studies involving 1009 patients.

The treatment also demonstrated a 1-year locoregional control rate of 72.3%, with severe adverse events occurring in less than 10% of patients, suggesting that SBRT is a safe and effective option for inoperable pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiation Therapy for Locally Advanced Pancreatic Cancer: A Systematic Review and Pooled Analysis of 19 Trials. Petrelli, F., Comito, T., Ghidini, A., et al.[2023]

The STEREOPAC trial aims to evaluate the effectiveness of adding isotoxic high-dose stereotactic body radiation (iHD-SBRT) to neoadjuvant chemotherapy in patients with borderline resectable pancreatic ductal adenocarcinoma (PDAC), involving 256 participants.

This study will assess key outcomes such as R0 resection rates and disease-free survival, helping to determine the optimal treatment sequence for improving oncological outcomes in PDAC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Bouchart, C., Navez, J., Borbath, I., et al.[2023]

In a phase 2 clinical trial involving 35 patients with borderline resectable (BR) and locally advanced (LA) pancreatic cancer, the combination of induction chemotherapy (gemcitabine and capecitabine) followed by stereotactic ablative radiation therapy (SABR) showed high rates of successful surgical resection, with 91.7% of surgeries resulting in R0 resection.

The treatment was well-tolerated, with no severe toxicities observed from SABR, and the study demonstrated promising overall survival rates, particularly for BR patients who underwent surgery, highlighting the potential efficacy of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Quan, K., Sutera, P., Xu, K., et al.[2023]

Stereotactic body radiotherapy (SBRT) is an effective treatment for pancreatic cancer, showing good tolerance and disease control, and may become a standard treatment option alongside chemoradiotherapy (CRT).

The combination of SBRT with chemotherapy could enhance treatment effects, although optimal doses and fractionation schedules for SBRT have yet to be established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy in pancreatic adenocarcinoma. de la Pinta, C.[2023]

Stereotactic body radiation therapy (SBRT) is emerging as a promising treatment for pancreatic cancer (PCA), particularly for patients with locally advanced, unresectable disease, offering potentially better tumor control compared to traditional chemotherapy and chemoradiation.

Early studies of SBRT using multiple doses (3-5) have shown favorable outcomes with improved tumor control and manageable toxicity rates, suggesting it may be a viable alternative to current standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy in pancreatic cancer: the new frontier. Moningi, S., Marciscano, AE., Rosati, LM., et al.[2014]

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Capecitabine and radiation therapy for advanced gastrointestinal malignancies. [2015]

2. England pubmed.ncbi.nlm.nih.gov

Comparison of capecitabine and 5-fluorouracil in chemoradiotherapy for locally advanced pancreatic cancer. [2021]

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Pancreatic cancer: are we moving forward yet? Highlights from the Gastrointestinal Cancers Symposium. Orlando, FL, USA. January 20th, 2007. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Protracted 5-fluorouracil infusion with concurrent radiotherapy as a treatment for locally advanced pancreatic carcinoma. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy as preoperative treatment in locally advanced unresectable pancreatic cancer patients: results of a feasibility study. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

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]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Fluoropyrimidines: a critical evaluation. [2017]

8. United States pubmed.ncbi.nlm.nih.gov

Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Potential of Xeloda in colorectal cancer and other solid tumors. [2017]

10. United States pubmed.ncbi.nlm.nih.gov

Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiation Therapy for Locally Advanced Pancreatic Cancer: A Systematic Review and Pooled Analysis of 19 Trials. [2023]

12. England pubmed.ncbi.nlm.nih.gov

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]

13. United States pubmed.ncbi.nlm.nih.gov

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]

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Stereotactic body radiotherapy in pancreatic adenocarcinoma. [2023]

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