Chemotherapy + Proton Therapy for Pancreatic Cancer

Recruiting at 2 trial locations

Overseen By Jasmine A Newman, BS

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Maryland, Baltimore

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Resectable cancer, Prior abdominal radiation, others

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

Compensation: Varies

Number of Visits: 5

Duration: 3 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safest dose of the chemotherapy drugs nab-paclitaxel and gemcitabine when combined with proton therapy, a type of radiation treatment, for advanced pancreatic cancer that has not spread to distant parts of the body. Participants will receive proton therapy daily for three weeks, with chemotherapy administered once a week during that period. Ideal candidates have pancreatic cancer that cannot be surgically removed due to solid tumor growth in specific blood vessels or areas. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking cancer treatment research.

Will I have to stop taking my current medications?

The trial requires that you stop taking strong CYP3A4 inhibitors or inducers 14 days before starting the study treatment. If you are on these medications, you will need to discontinue them.

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

Research has shown that gemcitabine, a chemotherapy drug used in this trial, is generally well-tolerated by patients. One study found that combining gemcitabine with nab-paclitaxel can extend the lives of pancreatic cancer patients, though some side effects like tiredness and low blood counts have been reported. These side effects are common with chemotherapy and are usually manageable.

Proton therapy, another component of this trial, is a specialized radiation treatment. It targets cancer cells more precisely, potentially leading to fewer side effects than traditional radiation. Although research on hypofractionated ablative proton therapy (a type of proton therapy given in higher doses over a shorter time) for pancreatic cancer is still developing, proton therapy is generally considered safe and is used for various cancers.

As this trial is in the early stages, it focuses on identifying the safest dose levels. Safety remains a top priority, and the treatment's effects are closely monitored. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining chemotherapy with proton therapy for pancreatic cancer because it offers a precise and potentially less harmful treatment option. Unlike traditional radiation therapy, proton therapy targets tumors more accurately, which may reduce damage to surrounding healthy tissues. This approach uses hypofractionated ablative proton therapy, delivering higher doses of radiation in fewer sessions, potentially enhancing effectiveness and shortening treatment time. Coupled with gemcitabine and nab-paclitaxel, this treatment aims to improve outcomes by using a powerful chemotherapy duo alongside the precision of proton therapy.

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

In this trial, participants will receive a combination of treatments. Studies have shown that gemcitabine, a drug for pancreatic cancer, is generally well-tolerated and can extend patient survival. One study found that 18% of patients using gemcitabine were alive after 12 months, compared to only 2% on a different treatment. Adding nab-paclitaxel to gemcitabine has also lowered the risk of cancer progression or death by 31%.

Additionally, this trial includes hypofractionated ablative proton therapy, a type of radiation treatment that targets tumors more precisely, protecting nearby healthy tissue. Although specific data on using hypofractionated ablative proton therapy for pancreatic cancer is limited, its precise targeting shows promise for treating this difficult-to-reach cancer. Overall, both treatments in this trial have shown potential to improve survival chances for pancreatic cancer patients. ^{2 3 6 7 8}

Who Is on the Research Team?

Jason Molitoris, MD

Principal Investigator

University of Maryland/Maryland Proton Treatment Center

Are You a Good Fit for This Trial?

This trial is for adults with nonmetastatic pancreatic cancer that can't be surgically removed. They should have good physical function (able to carry out daily activities) and adequate blood counts, kidney, and liver functions. Pregnant or breastfeeding individuals, those who've had certain prior treatments or surgeries for pancreatic cancer, or have specific genetic conditions are excluded.

Inclusion Criteria

My diagnosis is pancreatic adenocarcinoma.

My scans show my tumor can't be surgically removed due to its location.

Your kidneys are working well enough to filter out waste from your blood.

Exclusion Criteria

You did not follow the doctor's instructions for the initial chemotherapy treatment.

I have moderate to severe nerve pain or damage. I also have Gilbert's disease or a specific genetic condition.

I am not currently using, nor have I used in the last 14 days, any strong CYP3A4 inhibitors or inducers.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive concurrent nab-paclitaxel and gemcitabine with hypofractionated ablative proton therapy

3 weeks

5 visits per week (in-person)

Surgery/Adjuvant Therapy

Surgery if resectable, followed by adjuvant chemotherapy or no further therapy; or chemotherapy if not resectable

Follow-up

Participants are monitored for safety, effectiveness, and survival status after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine
• Hypofractionated Ablative Proton Therapy

Trial Overview The study aims to find the highest dose of nab-paclitaxel and gemcitabine chemotherapy drugs that's safe when given with a type of targeted radiation called hypofractionated ablative proton therapy over three weeks to treat advanced pancreatic cancer.

How Is the Trial Designed?

Group I: Pancreatic Proton Therapy With Concurrent Gem + Nab-paclitaxel Experimental Treatment 2 Interventions

Part I: Gemcitabine + nab-paclitaxel: • Administered per institutional standard every 7 days for 3 weeks Part II: Hypofractionated ablative pancreatic proton radiation therapy 67.5 Gy fractions once per day Monday - Friday for 3 weeks, for a total of 15 fractions. Part III: Surgery, if resectable, then adjuvant chemo per discretion of MD or no further therapy OR Chemo per discretion of MD if not resectable

Gemcitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Published Research Related to This Trial

In a study involving 9 patients with locally advanced pancreatic cancer, hypofractionated radiotherapy at 45 Gy in 15 fractions was well-tolerated, with no dose-limiting toxicities observed, allowing for timely initiation of full-dose gemcitabine chemotherapy.

However, the lower dose of 40 Gy in 8 fractions resulted in significant side effects, preventing timely chemotherapy initiation in most patients, indicating that this regimen is not feasible for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of hypofractionated radiotherapy followed by systemic chemotherapy with full-dose gemcitabine in patients with unresectable locally advanced pancreatic cancer. Furuse, J., Ishii, H., Kawashima, M., et al.[2022]

The hyperfractionated accelerated radiotherapy (HART) combined with gemcitabine showed a median survival of 12.9 months for patients with unresectable pancreatic cancer, which is slightly better than the 11.3 months observed with standard-fractionated radiotherapy (SFRT).

HART required significantly fewer treatment days (35.5 days) compared to SFRT (41.3 days) while maintaining similar toxicity profiles and response rates, indicating it is a more efficient treatment option without compromising safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of hyper-fractionated accelerated and standard fractionated radiotherapy with concomitant low-dose gemcitabine for unresectable pancreatic cancer. Maemura, K., Shinchi, H., Noma, H., et al.[2022]

In a systematic review of four studies involving 336 participants, combining gemcitabine with radiotherapy did not improve overall survival or progression-free survival compared to gemcitabine alone.

However, the addition of radiotherapy led to a higher incidence of severe side effects, such as anemia and fatigue, indicating that this combination may not be safe or beneficial for patients with pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is concomitant radiotherapy necessary with gemcitabine-based chemotherapy in pancreatic cancer? Zhang, X., Huang, HJ., Feng, D., et al.[2022]

Proton radiotherapy offers a promising approach for treating pancreatic carcinoma by delivering high doses of radiation directly to tumors while minimizing damage to surrounding healthy organs, which can reduce treatment toxicity.

Combining proton radiotherapy with improved chemotherapy regimens is essential for enhancing local-regional control of pancreatic cancer, potentially leading to better overall patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton beam radiotherapy for pancreas cancer. Rutenberg, MS., Nichols, RC.[2020]

The study involved 22 patients with Stage II and III pancreatic adenocarcinoma, and the treatment regimen of gemcitabine followed by concurrent gemcitabine and radiation was well tolerated, with no toxic deaths reported and manageable side effects.

After a median follow-up of 15 months, the median overall survival was 15 months, indicating that this treatment approach is feasible and may provide a foundation for further investigation into its effectiveness in improving outcomes for pancreatic cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative adjuvant gemcitabine and concurrent radiation after curative resection of pancreatic head carcinoma: a phase II study. Van Laethem, JL., Demols, A., Gay, F., et al.[2022]

In a study of 91 patients with inoperable pancreatic cancer treated with gemcitabine-concurrent proton radiotherapy (GPT), nearly 50% developed radiation-induced ulcers in the stomach and duodenum after treatment.

No cases of gastrointestinal hemorrhage or perforation were observed, suggesting that while GPT can lead to significant ulceration, it may not result in more severe acute GI complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upper gastrointestinal complications associated with gemcitabine-concurrent proton radiotherapy for inoperable pancreatic cancer. Takatori, K., Terashima, K., Yoshida, R., et al.[2022]

In a phase 2 study involving 49 patients with locally advanced pancreatic cancer, the combination of gemcitabine and fractionated stereotactic body radiotherapy (SBRT) resulted in low rates of late gastrointestinal toxicity, with only 11% experiencing grade ≥ 2 complications.

Patients reported significant pain relief and maintained stable quality of life scores after treatment, with a median overall survival of 13.9 months and a 78% rate of freedom from local disease progression at one year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 multi-institutional trial evaluating gemcitabine and stereotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma. Herman, JM., Chang, DT., Goodman, KA., et al.[2022]

Gemcitabine (Gemzar) has been shown to provide a survival benefit and improve quality of life for patients with advanced pancreatic cancer compared to traditional 5-FU chemotherapy.

The review suggests that gemcitabine combined with biomodulated 5-FU should be considered the standard palliative treatment for advanced pancreatic cancer, serving as a benchmark for future treatment comparisons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of gemcitabine alone and in combination in the treatment of pancreatic cancer. Oettle, H., Arnold, D., Hempel, C., et al.[2022]

The maximum tolerated dose (MTD) of weekly gemcitabine in combination with radiation therapy for pancreatic cancer was determined to be 250 mg/m2, with only one patient experiencing dose-limiting toxicity at lower doses.

The treatment showed a partial response rate of 29% and a median survival time of 13.7 months, indicating potential efficacy that warrants further investigation in phase-II trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy in patients with pancreatic carcinoma: phase-I study with a fixed radiation dose and escalating doses of weekly gemcitabine. Oya, N., Shibuya, K., Sakamoto, T., et al.[2022]

In a study of 22 patients with advanced pancreatic cancer, concurrent treatment with full-dose gemcitabine and limited-field radiotherapy was feasible, with 72% of patients completing the treatment regimen.

The treatment resulted in a 32% response rate and a median survival time of 16 months, with a notable 78% survival rate at one year for patients who underwent surgery after preoperative chemoradiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent chemoradiotherapy for advanced pancreatic cancer: 1,000 mg/m2 gemcitabine can be administered using limited-field radiotherapy. Yamazaki, H., Nishiyama, K., Koizumi, M., et al.[2022]

In a Phase II study involving 28 patients with unresectable locally advanced pancreatic cancer, the combination of weekly Gemcitabine and external beam radiotherapy was found to be safe, with 86% of patients completing the treatment despite some experiencing significant toxicities.

The treatment resulted in a median survival time of 10.3 months, with 21% of patients showing a partial response and 57% maintaining stable disease, indicating potential efficacy in managing this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of gemcitabine in combination with radiation therapy in patients with localized, unresectable, pancreatic cancer: a Hoosier Oncology Group study. Cardenes, HR., Moore, AM., Johnson, CS., et al.[2022]

Citations

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Gemcitabine Therapy in Patients with Advanced Pancreatic ... This study demonstrated results of the low toxicity and the good compliance of gemcitabine treatment in patients with advanced pancreatic cancer.

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The clinical outcomes of adjuvant gemcitabine plus S-1 in ... The 2-year survival rate was 27.3% in the gemcitabine monotherapy group, compared to 67.3% in the GS combination group in the Stage II and III ...

8. tandfonline.com tandfonline.com/doi/full/10.1080/1120009X.2023.2190712

Clinical outcome and safety profile of metastatic pancreatic ... It has been reported that the five-year survival rate is less than 8% for metastatic pancreatic cancer (mPC) [Citation4]. The optimal regimen is not well ...