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

Trial Summary

What is the purpose of this trial?

The prognosis for patients with localized pancreatic adenocarcinoma who are not surgical candidates is poor. Patients characterized as having "borderline resectable" disease treated with preoperative chemo-radiotherapy fair somewhat better - although many of these patients are not converted to resectability. It may be argued that intensification of local and regional therapy might 1.) Increase the share of patients able to undergo curative surgery and 2.) Improve the local disease control interval and extend survival for patients who remain unresectable. Therefore, the purpose of this research study is to determine if an increase in the number of surgical resection pancreatic adenocarcinoma is higher than historical data by using a combined treatment of proton radiation with capecitabine (oral chemotherapy).

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.

What data supports the effectiveness of the treatment involving proton radiation and capecitabine for pancreatic cancer?

Research shows that using proton radiation and capecitabine together can be effective for pancreatic cancer, as studies have evaluated their safety and effectiveness in making surgery possible for initially unresectable cases and improving outcomes in resectable cases. ^{1 2 3 4 5}

Is proton radiation with capecitabine safe for pancreatic cancer patients?

Studies show that using proton radiation with capecitabine is generally safe for pancreatic cancer patients, with research focusing on its use before and after surgery. Safety evaluations have been conducted in various trials, including those for other cancers, indicating it is well-tolerated in humans. ^{1 2 3 4 6}

How is the treatment of proton radiation and capecitabine unique for pancreatic cancer?

This treatment combines proton radiation, which targets tumors more precisely while sparing surrounding healthy tissues, with capecitabine, a chemotherapy drug taken orally. This approach is particularly beneficial for pancreatic cancer, where the pancreas is close to sensitive organs, making it a promising option for both resectable and unresectable tumors. ^{1 2 3 7 8}

Research Team

Romaine C. Nichols, MD

Principal Investigator

UF Health Proton Therapy Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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 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]

References

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

Feasibility of pancreatectomy following high-dose proton therapy for unresectable pancreatic cancer. [2020]

2. United States 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. [2022]

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

Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. [2022]

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

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

6. England pubmed.ncbi.nlm.nih.gov

Capecitabine based postoperative accelerated chemoradiation of pancreatic carcinoma. A dose-escalation study. [2018]

7. China pubmed.ncbi.nlm.nih.gov

Proton therapy for pancreatic cancer. [2020]

8. United States 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. [2015]