Combined Radiation and Chemotherapy for Pancreatic Cancer

Overseen By Dana B Kaplin, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Disqualifiers: Previous radiation, Duodenal invasion, 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)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat pancreatic cancer using intraoperative radiation therapy (IORT) during surgery. Researchers aim to determine its safety for individuals whose cancer remains confined to the pancreas and who are already receiving chemotherapy and radiation. It targets those managing pancreatic cancer with treatments like chemotherapy and radiation and are now considering surgery. Participants should have cancer that hasn’t spread beyond the pancreas and be eligible for specific treatments at Johns Hopkins University. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Do I need to stop my current medications for this trial?

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

What prior data suggests that intraoperative radiation therapy is safe for pancreatic cancer patients?

Research has shown that intraoperative radiation therapy (IORT) is generally well-tolerated by patients. One study found that using a low-energy X-ray for IORT was practical, and patients managed it well. Another study highlighted that IORT can target radiation to areas where cancer is most likely to return while protecting nearby organs. Increasing the radiation dose with IORT resulted in only minor side effects to important organs like the stomach and kidneys. Overall, these findings suggest that IORT safely delivers focused radiation treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for pancreatic cancer, which typically involve external beam radiation therapy and systemic chemotherapy, Intraoperative Radiation Therapy (IORT) is delivered directly to the tumor site during surgery. This direct application allows for a higher dose of radiation to be concentrated precisely where it's needed, minimizing damage to surrounding healthy tissues. Researchers are excited about IORT because it could potentially enhance the effectiveness of treatment by delivering a powerful radiation dose in a single session, possibly improving outcomes and reducing the overall treatment time compared to traditional approaches.

What evidence suggests that intraoperative radiation therapy is effective for pancreatic cancer?

Research has shown that intraoperative radiation therapy (IORT), which participants in this trial will receive, can be effective for treating pancreatic cancer. A study that combined results from multiple sources found that IORT improves local control of the cancer and extends survival in patients whose cancer can be surgically removed. Many patients also experienced less pain and better cancer control. Specifically, almost 95% of patients who had pain before treatment reported improvement after receiving IORT. These findings suggest that IORT could be a promising option for managing pancreatic cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Amol Narang, MD

Principal Investigator

JHU, School of Medicine, SKCCC

Are You a Good Fit for This Trial?

This trial is for adults over 18 with localized pancreatic cancer who can have surgery after chemotherapy and targeted radiation therapy (SBRT). They must be fit enough for the treatment, able to give consent, and not pregnant or causing pregnancy. People with tumors in certain parts of the pancreas, previous similar treatments, or unable to follow the study plan are excluded.

Inclusion Criteria

I am receiving initial treatment with a combination of chemotherapy drugs.

I am eligible for a surgery assessment at JHU.

My pancreatic cancer is considered operable according to NCCN guidelines.

Exclusion Criteria

My cancer has spread beyond the pancreas.

I cannot have the Whipple procedure.

You are currently participating in another study with a drug or device that could affect the results of this clinical trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive multi-agent chemotherapy as part of the standard of care treatment for pancreatic adenocarcinoma

8-12 weeks

Stereotactic Body Radiation Therapy (SBRT)

Participants undergo SBRT as part of the standard of care treatment for pancreatic adenocarcinoma

1-2 weeks

Surgical Resection with Intraoperative Radiation Therapy (IORT)

Participants undergo surgical resection of the tumor with a single dose of 15 Gy IORT targeting the Triangle Volume

During surgery

Follow-up

Participants are monitored for safety and effectiveness after treatment, including evaluation of acute and late post-operative toxicity

36 months

What Are the Treatments Tested in This Trial?

Interventions

• Intraoperative Radiation Therapy (IORT)

Trial Overview The trial tests if adding intraoperative radiation therapy (IORT) right after SBRT and before surgery is safe for patients with pancreatic cancer. It's given during an operation at Johns Hopkins University (JHU) following specific guidelines.

How Is the Trial Designed?

Group I: Intra Operative Radiation Therapy (IORT) Group Experimental Treatment 1 Intervention

The IORT group is the single arm of this study. Enrolled patients who undergo standard of care treatment will also receive a study treatment of High Dose Rate (HDR) Intra Operative Radiation Therapy.

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Published Research Related to This Trial

A treatment program combining intraoperative electron beam radiation therapy (IOERT) with external beam radiation and chemotherapy resulted in long-term survival for 8 out of 150 patients with unresectable pancreatic cancer, indicating potential efficacy for this approach.

Survival rates were significantly better for patients with smaller tumors, as those treated with a small-diameter applicator had 2- and 3-year survival rates of 27% and 17%, while larger applicators showed no long-term survival, suggesting that tumor size is a critical factor in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term results of intraoperative electron beam irradiation (IOERT) for patients with unresectable pancreatic cancer. Willett, CG., Del Castillo, CF., Shih, HA., et al.[2019]

Intraoperative radiation therapy (IORT) with electrons was administered to 52 patients with locally advanced pancreatic cancer, showing acceptable acute and chronic tolerance to the treatment.

Local progression of cancer was infrequent (7% in evaluable patients), but there was no significant improvement in median or long-term survival, likely due to the high rates of liver and peritoneal metastases associated with pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative and external beam irradiation +/- 5-FU for locally advanced pancreatic cancer. Gunderson, LL., Martin, JK., Kvols, LK., et al.[2019]

Intraoperative electron beam radiation therapy (IOERT) allows for a higher total radiation dose to be delivered directly to tumors during surgery, potentially improving local tumor control in patients with resectable or locally advanced pancreatic cancer.

IOERT is believed to have a biological effectiveness equivalent to at least double the dose of conventional radiation treatments, making it a promising approach when combined with surgery, external beam radiation, and chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperatic electron beam irradiation in pancreatic cancer. Willett, CG., Warshaw, AL.[2019]

In a study of 49 patients with unresectable pancreatic cancer, the combination of intraoperative radiation therapy (IORT) and perioperative chemotherapy resulted in a median survival time of 16 months and a 2-year survival rate of 22%, indicating potential effectiveness in managing this challenging condition.

The treatment showed a low incidence of perioperative mortality (0%) and manageable early and late complications, primarily gastrointestinal, suggesting that this multimodal approach is relatively safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined intraoperative radiation and perioperative chemotherapy for unresectable cancers of the pancreas. Mohiuddin, M., Regine, WF., Stevens, J., et al.[2022]

Electron beam intraoperative radiation therapy (IORT) combined with external radiation therapy was used to treat 29 patients with localized, unresectable pancreatic carcinoma, resulting in a median survival of 16.5 months and 14 patients currently alive, with 11 showing no evidence of disease after treatment.

Patients treated with misonidazole prior to IORT showed no local recurrences, while those not treated with it had a higher rate of local recurrence, suggesting a potential benefit of misonidazole, although further studies are needed to confirm this finding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative electron beam irradiation for patients with unresectable pancreatic carcinoma. Shipley, WU., Wood, WC., Tepper, JE., et al.[2019]

In a study of 115 patients with locally advanced pancreatic cancer, intra-operative radiotherapy (IORT) was found to be a safe and reliable treatment, with major complications including gastroparesis syndrome (10.4%), hemorrhage (3.5%), and abdominal infection (2.6%).

Despite these complications, the overall prognosis was relatively good, as all patients except one survived, indicating that IORT can be an effective option for managing this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Early complications of intra-operative radiotherapy in locally advanced pancreatic cancer]. Zhang, J., Che, X., Chen, Y., et al.[2023]

Intraoperative radiotherapy (IORT) was safely administered to 13 patients with pancreatic cancer, with no serious complications or wound healing issues reported, indicating a good safety profile for this treatment method.

Initial results suggest that IORT may provide significant relief from pancreatic pain, although it is still too early to determine its impact on overall survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Intraoperative radiation treatment of carcinoma of the pancreas. Initial clinical results]. Bodner, E., Glaser, K., Aufschnaiter, M., et al.[2006]

Intraoperative radiotherapy (IORT) is a safe and effective method for delivering high doses of radiation to patients with unresectable pancreatic cancer, significantly reducing abdominal and back pain, although it does not improve overall prognosis on its own.

Combining IORT with external beam radiotherapy (EBRT) has shown better local control rates compared to EBRT alone, particularly in patients with lower CA 19-9 levels, suggesting this combination could be a recommended treatment for localized pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative radiotherapy and hyperthermia for unresectable pancreatic cancer. Shibamoto, Y., Nishimura, U., Abe, M.[2006]

Intraoperative radiotherapy (IORT) using high-energy electrons was tested in 23 patients with pancreatic carcinoma, but it resulted in more complications compared to patients who did not receive IORT (36 patients).

While IORT may suggest potential benefits for prolonged survival after curative surgeries, the evidence is inconclusive due to the small sample size, and further research is needed, particularly in combination with postoperative radiochemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of intraoperative radiotherapy on postoperative follow-up of pancreas cancer]. Kasperk, R., Ammon, J., Schumpelick, V.[2006]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5223572/

Intraoperative radiation therapy (IORT) in pancreatic cancer Series of patients with unresectable pancreatic cancer show that most patients experience pain relief and improved local control. In select ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1053429625000645

Review Article Intraoperative Radiation for Pancreatic Cancer The authors also reported that in 117 patients who complained of pain prior to treatment, nearly 95% had some improvement in their pain after IORT including 74 ...

3. cancerbiomed.org cancerbiomed.org/content/22/1/67

Safety and efficacy of intraoperative radiation therapy using ... A meta-analysis has revealed that IORT improves locoregional control and overall survival (OS) in patients with resectable pancreatic cancer ...

4. intraop.com intraop.com/pancreatic-cancer-treatment-iort/

Pancreatic Cancer Treatment with Mobetron Mobetron electron IORT treatment may increase the overall survival rates of patients with locally advanced, unresectable pancreatic cancer.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1356915/

Long-term Results of Intraoperative Electron Beam ... Conclusions: A treatment strategy employing IOERT has resulted in long-term survival in 8 of 150 patients with unresectable pancreatic cancer. Survival benefit ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11795264/

Safety and efficacy of intraoperative radiation therapy using a ... This study supports use of IORT with a 50 kV X-ray source in treating RPC. IORT using a low-energy X-ray source was well-tolerated and feasible.

7. thegreenjournal.com thegreenjournal.com/article/S0167-8140(20)30174-2/fulltext

ESTRO IORT Task Force/ACROP recommendations for ... Highlights: Radiation dose-escalation with IOERT feasible with limited toxicity to stomach, colon, kidneys and duodenum.

8. eymj.org eymj.org/DOIx.php?id=10.3349/ymj.2022.63.5.405

Intraoperative Radiotherapy for Resectable Pancreatic ... We evaluated the safety, feasibility, and early treatment outcomes of intraoperative radiotherapy (IORT) using a low-energy X-ray source.