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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treat pancreatic cancer that has spread to nearby tissues or lymph nodes. It tests whether combining targeted radiation therapy (stereotactic body radiation therapy) and chemotherapy, with or without the drug zoledronic acid, can improve outcomes. The radiation aims to shrink tumors with precision, while the drugs help stop cancer growth. The trial seeks individuals with locally advanced pancreatic cancer who have recently undergone chemotherapy and cannot currently undergo surgery. Participants should expect treatment over several weeks, followed by surgery if the tumor becomes operable. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown varying levels of safety for the treatments tested in this trial. Stereotactic Body Radiation Therapy (SBRT) is generally safe and well-tolerated, with research indicating few serious side effects, making it a promising option for patients with pancreatic cancer.

Safety information is also available for the chemotherapy drugs fluorouracil (often called 5-FU) and capecitabine. Fluorouracil is commonly used to treat pancreatic cancer and is effective with manageable side effects. Similarly, capecitabine is FDA-approved for various cancers, including stomach and breast cancer, and can sometimes cause infections that require immediate treatment.

Zoledronic acid, another component of the trial, is typically used to reduce symptoms in cancer patients and is considered safe when used correctly. It can cause some side effects, but these are usually not severe.

Overall, the treatments in this trial have been used in other settings with a good safety record. Awareness of potential side effects and discussing any concerns with healthcare providers is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for pancreatic cancer because they combine targeted radiation with chemotherapy and a potential bone-strengthening agent. The use of stereotactic body radiation therapy (SBRT) allows for precisely targeted radiation in fewer sessions, potentially reducing damage to surrounding healthy tissue compared to traditional radiation therapy. Arm A leverages this precision along with standard chemotherapy agents, Capecitabine or Fluorouracil, enhancing their effectiveness. Arm B introduces Zoledronic acid, typically used to strengthen bones, which might also help the body better tolerate and respond to cancer treatment. This combination of therapies aims to improve surgical outcomes and overall effectiveness, offering new hope in the fight against pancreatic cancer.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research has shown that stereotactic body radiation therapy (SBRT) can effectively treat pancreatic cancer. Studies suggest patients have a median survival time of about 14 months, with an 85% chance of controlling the cancer in the treated area for at least one year. In this trial, participants in Arm A will receive SBRT combined with either capecitabine or fluorouracil (5-FU), both of which have demonstrated positive results in patients with advanced pancreatic cancer. Participants in Arm B will receive zoledronic acid in addition to the treatments in Arm A. Zoledronic acid might increase cancer cells' sensitivity to radiation, but its effect on survival remains under investigation. Overall, these combined treatments show promise in managing pancreatic cancer. ^{5 6 7 8 9}

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

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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XELODA® (capecitabine) tablets, for oral use Pancreatic Cancer. The safety of XELODA for the adjuvant treatment of adults with pancreatic adenocarcinoma as a component of a combination chemotherapy ...

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Capecitabine (Xeloda®) Capecitabine can increase your risk of getting an infection. An infection is an emergency if you are having chemotherapy, and needs treating straight away.

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FDA Approval Summary: Capecitabine Labeling Update ... The safety of capecitabine for the treatment of adults with unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer as a component ...