Clinical trial NCT04090463: IORT on Borderline Resectable Pancreatic Cancer
Official title: A Phase II Study of Primary Chemotherapy, Stereotactic Body Radiation Therapy, and Intraoperative Radiation Therapy in Borderline Resectable Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
Conditions: Borderline Resectable Pancreatic Cancer
Keywords: Pancreatic cancer
Borderline resectable pancreatic cancer
Intraoperative radiotherapy (IORT)
Total neoadjuvant therapy
Lead sponsor: Universita di Verona
Sponsor class: OTHER
First posted: 2019-09-16
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II study investigates the efficacy of IORT for patients with borderline resectable pancreatic cancer. The purpose of the study is to investigate whether the addition of IORT, after FOLOFIRINOX-base chemotherapy, and SBRT, increases the 3-year survival rate. A total of 101 patients will be enrolled, and these patients will receive IORT of 10 to 20 Gy, according to the resection status (to the tumor bed after resection, or to the tumor in situ in case of non-resection).

Detailed description: Treatment outcomes of borderline resectable pancreatic cancer are still poor even after completion of FOLFIRINOX-based chemotherapy and radical resection. A growing body of literature is demonstrating that Stereotactic body radiation therapy (SBRT) and Intraoperative radiotherapy (IORT), within a multimodal approach, allow to obtain better oncological outcome, at the price of low to negligible rates of morbidity and mortality. The investigators hypothesize that a "total neoadjuvant" scenario, with the best current therapy, based on up to 6 months of FOLFIRINOX (minimum 4), SBRT and IORT (in situ or after surgery) would increase the disease-specific survival of borderline resectable pancreatic cancer patients. An historical cohort will be used as a comparison group.

Considering the intention-to-treat design and the institutional rates of chemotherapy completion and exploration/resection of borderline resection pancreatic cancer patients, a total of 100 patients will be enrolled in this phase II trial. Patients submitted to IORT, will receive IORT of 10 to 20 Gy according to the resection status (to the tumor bed after resection, or to the tumor in situ in case of non-resection).

Eligibility criteria: Inclusion Criteria:

* • Biopsy-proven, previously untreated borderline resectable PC, defined according to the NCCN guidelines v1.2019;

  * Age 18-80 years;
  * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
  * Adequate bone marrow function (absolute neutrophil count ≥1500 per cubic millimeter; platelet count ≥100.000 per cubic millimeter; hemoglobin level ≥10 g per deciliter), liver function (serum total bilirubin level ≤1.5 times the upper limit of the normal range), and renal function (creatinine clearance ≥50 ml per minute);
  * Ability to understand the characteristics of the clinical trial;
  * Written informed consent.

Exclusion Criteria:

* • Ampullary, biliary, or duodenal adenocarcinoma; pancreatic adenocarcinoma in the background of an intraductal papillary mucinous neoplasia (IPMN), other uncommon pancreatic adenocarcinomas (acinar-cell, squamous, giant-cell osteoclastic-like);

  * Invasive cancer in the last 5 years requiring radiation therapy to the upper abdomen or chemotherapy;
  * Symptomatic heart failure or coronary artery disease;
  * Pregnant or lactating women;
  * Impaired mental state or language problems.

Primary outcomes:
measure: Disease-specific survival
timeFrame: 36 months
Secondary outcomes:
measure: Progression-free survival
timeFrame: 36 months
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: 36 months
measure: Rate of margin-free surgery
timeFrame: 30 days
measure: Rate of surgical complications
timeFrame: Up to 90 days after surgery
measure: Resection rate
timeFrame: Intraoperative
Other outcomes:
Locations:
city: Verona
country: Italy
facility: General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona Hospital
Study officials:
References:
citation: Palta M, Willett C, Czito B. The role of intraoperative radiation therapy in patients with pancreatic cancer. Semin Radiat Oncol. 2014 Apr;24(2):126-31. doi: 10.1016/j.semradonc.2013.11.004.
citation: Krempien R, Roeder F. Intraoperative radiation therapy (IORT) in pancreatic cancer. Radiat Oncol. 2017 Jan 10;12(1):8. doi: 10.1186/s13014-016-0753-0.
citation: Cai S, Hong TS, Goldberg SI, Fernandez-del Castillo C, Thayer SP, Ferrone CR, Ryan DP, Blaszkowsky LS, Kwak EL, Willett CG, Lillemoe KD, Warshaw AL, Wo JY. Updated long-term outcomes and prognostic factors for patients with unresectable locally advanced pancreatic cancer treated with intraoperative radiotherapy at the Massachusetts General Hospital, 1978 to 2010. Cancer. 2013 Dec 1;119(23):4196-204. doi: 10.1002/cncr.28329. Epub 2013 Sep 4.
citation: Murphy JE, Wo JY, Ryan DP, Jiang W, Yeap BY, Drapek LC, Blaszkowsky LS, Kwak EL, Allen JN, Clark JW, Faris JE, Zhu AX, Goyal L, Lillemoe KD, DeLaney TF, Fernandez-Del Castillo C, Ferrone CR, Hong TS. Total Neoadjuvant Therapy With FOLFIRINOX Followed by Individualized Chemoradiotherapy for Borderline Resectable Pancreatic Adenocarcinoma: A Phase 2 Clinical Trial. JAMA Oncol. 2018 Jul 1;4(7):963-969. doi: 10.1001/jamaoncol.2018.0329.
citation: Paiella S, Malleo G, Simoni N, Micera R, Guariglia S, Cavedon C, Marchegiani G, Esposito A, Landoni L, Casetti L, Tuveri M, Milella M, Secchettin E, Manzini G, Bovo C, De Pastena M, Fontana M, Salvia R, Mazzarotto R, Bassi C. A phase II trial proposal of total neoadjuvant treatment with primary chemotherapy, stereotactic body radiation therapy, and intraoperative radiation therapy in borderline resectable pancreatic adenocarcinoma. BMC Cancer. 2021 Feb 16;21(1):165. doi: 10.1186/s12885-021-07877-7.