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

Trial Summary

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 data supports the effectiveness of the treatment Intraoperative Radiation Therapy (IORT) for pancreatic cancer?

Research suggests that IORT, when combined with other treatments like external beam radiotherapy (EBRT), can help control local tumor growth and improve pain management in pancreatic cancer patients, although it may not significantly extend survival time. ^{1 2 3 4 5}

Is intraoperative radiation therapy (IORT) safe for humans?

Intraoperative radiation therapy (IORT) for pancreatic cancer has been shown to be generally safe, with studies reporting no serious early complications related to the radiation. Sensitive tissues like the stomach and intestines are protected during the procedure to prevent damage, and both acute and chronic tolerance have been acceptable. ^{3 4 6 7 8}

How does the combined radiation and chemotherapy treatment for pancreatic cancer differ from other treatments?

This treatment is unique because it combines intraoperative radiation therapy (IORT), which delivers high doses of radiation directly to the tumor during surgery, with perioperative chemotherapy. This approach aims to improve local and systemic tumor control, potentially offering better pain relief and survival outcomes compared to traditional methods that do not use IORT. ^{1 2 3 5 9}

What is the purpose of this trial?

This study is designed to investigate the safety of intraoperative radiation therapy (IORT) in patients with localized pancreatic cancer undergoing surgical resection after neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT).

Research Team

Amol Narang, MD

Principal Investigator

JHU, School of Medicine, SKCCC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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 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]

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]

References

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

Long-term results of intraoperative electron beam irradiation (IOERT) for patients with unresectable pancreatic cancer. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

[Effect of intraoperative radiotherapy on postoperative follow-up of pancreas cancer]. [2006]

3. Germany pubmed.ncbi.nlm.nih.gov

[Intraoperative radiation treatment of carcinoma of the pancreas. Initial clinical results]. [2006]

4. Greece pubmed.ncbi.nlm.nih.gov

Intraoperative radiotherapy and hyperthermia for unresectable pancreatic cancer. [2006]

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

Combined intraoperative radiation and perioperative chemotherapy for unresectable cancers of the pancreas. [2022]

6. China pubmed.ncbi.nlm.nih.gov

[Early complications of intra-operative radiotherapy in locally advanced pancreatic cancer]. [2023]

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

Intraoperative and external beam irradiation +/- 5-FU for locally advanced pancreatic cancer. [2019]

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

Intraoperatic electron beam irradiation in pancreatic cancer. [2019]

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

Intraoperative electron beam irradiation for patients with unresectable pancreatic carcinoma. [2019]