Clinical trial NCT05141513: Intraoperative Radiation Therapy After Stereotactic Body Radiation Therapy and Chemotherapy in Treatment of Pancreatic Adenocarcinoma
Official title: A Safety Study of Intraoperative Radiation Therapy Following Stereotactic Body Radiation Therapy and Multi-agent Chemotherapy in the Treatment of Localized Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pancreatic Cancer
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
First posted: 2021-12-02
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a prospective, single institution, single arm pilot study to evaluate the safety and feasibility of implementing IORT in patients with non-metastatic Pancreatic adenocarcinoma (PDAC) who have been treated with neoadjuvant chemotherapy and SBRT and who are undergoing surgical resection.
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: Standard of care treatment for patients with non-metastatic pancreatic adenocarcinoma (PDAC) includes chemotherapy and Stereotactic Body Radiation Treatment (SBRT) followed by surgical resection of the tumor with or without Intra-Operative Radiation Therapy (IORT).

There is some evidence from other research studies suggesting that adding radiation treatment during the surgical resection may improve local control of the cancer. The use of IORT plus surgical resection can be used to treat pancreatic cancer and is done on a case by case basis at Johns Hopkins.

The department of Radiation Oncology has developed a program using a High Dose Rate-IORT (HDR-IORT). The HDR-IORT makes it possible to deliver concentrated radiation dose at the surface of the tumor.

Our team has shown in previous studies that the majority of cancer cells that remain after treatment are located around the area of the pancreas called the "Triangle Volume" (TV). This region contains blood vessels, lymphatic vessels, and nerves, and is at high risk of containing cancer cells. This region is difficult to treat with SBRT alone because of being close to normal, healthy organs. Therefore, this study involves using IORT to treat the TV to a therapeutic radiation dose.

The part of the treatment that is considered research is:

* Giving one dose of 15 Gy during the surgery using IORT to deliver radiation, and
* Targeting the larger area around the pancreas called the TV

The goal of this study is to determine safety of this added treatment which will be assessed at 3 months after the surgery is completed.

Eligibility criteria: Inclusion Criteria:

1. Age \> 18 years old
2. Resectable/BRPC/LAPC as defined by NCCN guidelines (Figure 1) as follows confirmed via CT, EUS, or other imaging modalities.
3. ECOG performance status 0-2
4. Subject or authorized representative, has been informed of the nature of the study and has provided written informed consent, approved by the appropriate Institutional Review Board (IRB) of the respective clinical site.
5. Candidate for SBRT at JHU
6. Upfront treatment with multi-agent chemotherapy
7. Candidate for surgical exploration at JHU

Exclusion Criteria:

1. Previous thoracic/abdominal radiation therapy
2. Unable to receive SBRT at JHU
3. Duodenal invasion detected on imaging which would exclude candidacy for SBRT
4. Tumor located in pancreatic body or tail
5. Unable to undergo Whipple procedure
6. Evidence of disease not localized to the pancreas
7. Any arterial reconstruction during surgery
8. Currently enrolled in another investigational drug or device trial that clinically interferes with this study
9. Unable to comply with study requirements or follow-up schedule
10. Women of child bearing potential or sexually active fertile men with partners who are women of child bearing potenital who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study

Primary outcomes:
measure: Acute post-operative toxicity of targeted IORT
timeFrame: 3 months
Secondary outcomes:
measure: Late post-operative toxicity of targeted IORT
timeFrame: 6 months
measure: Late post-operative toxicity of targeted IORT
timeFrame: 12 months
measure: Late post-operative toxicity of targeted IORT
timeFrame: 24 months
measure: Late post-operative toxicity of targeted IORT
timeFrame: 36 months
measure: Median local-progression free survival (LPFS) from IORT
timeFrame: 6 months
measure: Median local-progression free survival (LPFS) from IORT
timeFrame: 12 months
measure: Median local-progression free survival (LPFS) from IORT
timeFrame: 24 months
measure: Median local-progression free survival (LPFS) from IORT
timeFrame: 36 months
measure: Median overall survival (OS) from IORT
timeFrame: 6 months
measure: Median overall survival (OS) from IORT
timeFrame: 12 months
measure: Median overall survival (OS) from IORT
timeFrame: 24 months
measure: Median overall survival (OS) from IORT
timeFrame: 36 months
measure: Median progression free survival (PFS) from IORT
timeFrame: 6 months
measure: Median progression free survival (PFS) from IORT
timeFrame: 12 months
measure: Median progression free survival (PFS) from IORT
timeFrame: 24 months
measure: Median progression free survival (PFS) from IORT
timeFrame: 36 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: JHU, School of Medicine, SKCCC
name: Amol Narang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Reddy AV, Hill CS, Zheng L, He J, Narang AK. A safety study of intraoperative radiation therapy following stereotactic body radiation therapy and multi-agent chemotherapy in the treatment of localized pancreatic adenocarcinoma: study protocol of a phase I trial. Radiat Oncol. 2022 Oct 28;17(1):173. doi: 10.1186/s13014-022-02145-9.