Proton Radiation for Pancreatic Cancer

Recruiting at 3 trial locations

Overseen By Edith Maritato

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Proton Collaborative Group

Must be taking: Capecitabine

Disqualifiers: Distant metastasis, Prior surgery, others

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

Duration: 6 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with pancreatic cancer that cannot be surgically removed. Researchers are combining proton radiation (also known as proton beam therapy) with oral chemotherapy (capecitabine) to determine if this approach can increase the number of patients eligible for surgery and improve survival rates. The trial seeks participants diagnosed with unresectable pancreatic cancer, who may also have a drainage tube for a bile duct blockage. This study aims to offer new hope for those facing this challenging condition. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to potentially groundbreaking advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that proton beam therapy, a type of radiation treatment, might be safer for patients than traditional photon therapy, potentially resulting in fewer side effects. One study found that most patients experienced only mild side effects, such as tiredness or nausea, occurring in about 78.7% of patients. More serious side effects were less common, appearing in about 21.3% of patients.

Capecitabine, a chemotherapy pill already used for other cancers, has a well-understood safety profile. It can cause side effects like hand-foot syndrome, where the skin on the hands and feet might peel or feel sore. However, doctors closely monitor these effects.

Overall, the combination of proton radiation and capecitabine is generally well-tolerated. Studies suggest it can be a relatively safe option for people with pancreatic cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of capecitabine and proton radiation for pancreatic cancer because it offers a more targeted approach than traditional radiation therapy. Unlike conventional radiation, proton radiation delivers high doses of radiation directly to the tumor while minimizing damage to surrounding healthy tissue. When paired with capecitabine, a chemotherapy drug that makes cancer cells more sensitive to radiation, this treatment has the potential to be more effective in shrinking tumors and increasing the chances of successful surgical removal. This innovative approach could lead to better outcomes and fewer side effects for patients.

What evidence suggests that proton radiation with capecitabine could be effective for pancreatic cancer?

This trial will evaluate the combination of proton radiation with capecitabine for treating pancreatic cancer. Research has shown that this combination may aid in treating pancreatic cancer. Studies have found that proton beam therapy (PBT) can extend the lives of patients with inoperable pancreatic cancer and has a safe level of side effects. Capecitabine, a pill, enhances the effectiveness of radiation treatments. Together, these treatments might enable the removal of previously inoperable tumors. Additionally, PBT can cause fewer side effects than conventional radiation, making it a potentially safer option. Early results suggest this combination could extend patients' lives and improve their quality of life. ^{1 2 3 4 6}

Who Is on the Research Team?

Romaine C. Nichols, MD

Principal Investigator

UF Health Proton Therapy Institute

Are You a Good Fit for This Trial?

This trial is for adults with pancreatic cancer that can't be removed by surgery, or they're not candidates for surgery. They must agree to use contraception and have certain blood counts and organ functions within specific ranges. People with distant cancer spread, prior abdominal radiation, active infections, previous surgeries on the pancreas, or other recent cancers aren't eligible.

Inclusion Criteria

Required pretreatment laboratory parameters:

Platelet count ≥ 100,000/mm3

Bilirubin < 2 mg/dl

Exclusion Criteria

I have been cancer-free for 5 years, except for non-melanoma skin or low-risk prostate cancer.

I have had radiation therapy to my abdomen before.

I have had surgery to remove a tumor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Proton radiation therapy with concomitant oral chemotherapy (capecitabine) on radiation days for 6 weeks

6 weeks

Surgical Evaluation

Surgical resection will be performed between 8 and 16 weeks if radiographic studies suggest operability

8-16 weeks post-treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a focus on surgical resection rate and overall survival

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Proton Radiation
• Surgical resection

Trial Overview The study tests if combining proton radiation therapy with oral chemotherapy (Capecitabine) increases the number of patients who can undergo curative surgery compared to past data. It also examines whether this approach improves control of local disease and survival rates in those who remain non-operable.

How Is the Trial Designed?

Group I: Proton Radiation with capecitabine Experimental Treatment 3 Interventions

The following will be performed in this group: Proton Radiation Therapy with concomitant oral chemotherapy, capecitabine taken on radiation treatment days for 6 weeks. A surgical resection will be performed between 8 and 16 weeks if radiographic studies suggest operability.

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?

Proton Collaborative Group

Lead Sponsor

Trials

10

Recruited

41,100+

University of Florida Health

Collaborator

Trials

10

Recruited

4,200+

Published Research Related to This Trial

The study demonstrated that short-course proton beam radiation combined with capecitabine is safe, with only 4.1% of patients experiencing grade 3 toxicity, well below the target of 20%.

Despite the treatment's safety, the study found that many patients had poor outcomes, with a median overall survival of 17 months and significant associations between certain biomarkers (like KRAS mutations and circulating CEA levels) and worse survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1/2 and biomarker study of preoperative short course chemoradiation with proton beam therapy and capecitabine followed by early surgery for resectable pancreatic ductal adenocarcinoma. Hong, TS., Ryan, DP., Borger, DR., et al.[2022]

In a study involving 15 patients with locally advanced pancreatic cancer, capecitabine combined with radiotherapy was found to be feasible, with a recommended dose of 800 mg/m2 bid for further evaluation.

While some patients experienced side effects like grade 3 diarrhea, the treatment showed potential efficacy with 20% achieving a partial response, suggesting that capecitabine could serve as a simpler alternative to intravenous fluorouracil for enhancing the effects of radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of capecitabine with concomitant radiotherapy for patients with locally advanced pancreatic cancer: expression analysis of genes related to outcome. Saif, MW., Eloubeidi, MA., Russo, S., et al.[2015]

In a study of 15 patients with initially unresectable pancreatic cancer treated with proton therapy and capecitabine, 5 patients successfully underwent pancreatectomy, demonstrating that surgical resection is feasible after high-dose proton therapy.

The median survival for the 5 patients who had surgery was 24 months, indicating that this treatment approach can lead to significant local control and acceptable surgical outcomes despite the initial unresectable diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of pancreatectomy following high-dose proton therapy for unresectable pancreatic cancer. Hitchcock, KE., Nichols, RC., Morris, CG., et al.[2020]

The study demonstrated that escalating the radiation dose to 55 Gy over five weeks, combined with a daily dose of capecitabine, can be safely administered to patients with resected pancreatic cancer, with no dose-limiting toxicities observed in 12 participants.

While some patients experienced mild side effects like grade 1-2 nausea and vomiting, the treatment regimen was well-tolerated, indicating a promising safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine based postoperative accelerated chemoradiation of pancreatic carcinoma. A dose-escalation study. Morganti, AG., Picardi, V., Ippolito, E., et al.[2018]

Proton radiotherapy offers a promising alternative to conventional radiotherapy for pancreatic cancer by delivering targeted doses to tumors while minimizing damage to surrounding sensitive organs, which is crucial given the pancreas's location.

The review highlights that proton therapy could significantly improve treatment outcomes for patients with both unresectable and marginally resectable pancreatic tumors, potentially changing how this cancer is managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton therapy for pancreatic cancer. Nichols, RC., Huh, S., Li, Z., et al.[2020]

In a study of 42 patients with metastatic or locally advanced pancreatic cancer, capecitabine demonstrated a clinical benefit response in 24% of patients, improving pain intensity and overall performance status.

Capecitabine was generally well tolerated, with a 9.5% objective response rate, suggesting it may be a viable treatment option for further evaluation in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. Cartwright, TH., Cohn, A., Varkey, JA., et al.[2022]

In a study of 44 previously untreated patients with advanced gastric cancer, capecitabine demonstrated an objective response rate of 34% and a median overall survival of 9.5 months, indicating its efficacy as a first-line treatment.

Capecitabine was generally well tolerated, with the most common side effects being hand-foot syndrome and nausea, and severe myelosuppression was not observed, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. Hong, YS., Song, SY., Lee, SI., et al.[2022]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7052755/

Proton beam radiotherapy for pancreas cancer - PMC The results of EORTC 40891 showed a strong trend toward improved survival with postoperative CRT, although it did not reach statistical significance (9).

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301624037696

Proton Beam Therapy for Pancreatic Tumors: A Consensus ... Proton beam therapy (PBT) may reduce toxicities compared to photon therapy. This consensus statement summarizes PBT's safe and optimal delivery for pancreatic ...

3. nature.com nature.com/articles/s41598-020-78875-1

Efficacy and feasibility of proton beam radiotherapy using ... PBT with the SIB technique showed promising OS for LAPC patients with a safe toxicity profile, and intensive combinations of PBT and chemotherapy could improve ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02598349

Proton Radiation for Unresectable, Borderline Resectable, ... The prognosis for patients with localized pancreatic adenocarcinoma who are not surgical candidates is poor. Patients characterized as having "borderline ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2331518023000306

Proton Therapy and Concomitant Capecitabine for Non ... One- and 2-year overall survival, progression-free survival, distant metastasis-free survival, and freedom from local progression rates were 61% and 31% (median ...

6. advancesradonc.com advancesradonc.com/article/S2452-1094(23)00079-9/fulltext

Proton Therapy for Unresectable and Medically Inoperable ... Grade 1 and 2 adverse events occurred in 78.7% and 21.3% of patients, respectively. Median overall survival, locoregional recurrence-free ...