Low-dose Radiotherapy Plus Chemotherapy With Gem-based Doublets and Stereotactic Radiotherapy for Advanced Pancreatic Cancer (ORCHESTRATE)

Low-dose Radiotherapy as a Chemo-potentiator of a Induction Chemotherapy Regimen With Gem-based Doublets and Stereotactic Body Radiotherapy for Locally Advanced Pancreatic Cancer

Aim of this study is to evaluate if low-dose radiotherapy (LDR) can intensify local effect of a chemotherapy regimen with Gem-based doublets administered sequentially with stereotactic body radiotherapy (SBRT) and to assess the safety and efficacy of this combined treatment on patients affected by locally advanced pancreatic adenocarcinoma (LAPC).

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Radiation: LDR; Drug: Gem-based doublets; Radiation: SBRT

• Study Type: Interventional
• Enrollment (Anticipated): 44
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bruno Meduri, MD; Phone Number: +393388878319; Email: brunomeduri@gmail.com

Study Locations

• Italy
  • MO
    • Modena, MO, Italy, 41121
      • Recruiting
      • Azienda Ospedaliero-Universitaria Policlinico di Modena
      • Contact: Bruno Meduri, MD; Phone Number: +393388878319; Email: brunomeduri@gmail.com
      • Principal Investigator: Bruno Meduri, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pathologically confirmed adenocarcinoma of the pancreas
• Patients with unresectable disease based on institutional standardized criteria of unresectability or patients whose disease appeared potentially resectable on axial CT imaging but were found unresectable at surgery
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. Age ≥ 18
• Patients with biliary or gastroduodenal obstruction must have drainage or surgical bypass prior to starting treatment
• Patients with radiographically assessable disease
• Adequate bone marrow, hepatic and renal function: -Hemoglobin >10.0 g/dL, absolute neutrophil count > 1.5 x 10^9/L, platelet count > 100 x 10^9/L. -Aspartate transaminase (AST or SGOT) and alanine transaminase (ALT or SGPT) should be ≤ 3 x upper limit of normal (ULN). -Total bilirubin < 2 mg/dL. Patients with elevated bilirubin due to obstruction should be stented and their bilirubin should decrease to < 2 mg/dL prior to study entry. - Creatinine < 3 mg/dL or Creatinine clearance > 40 mL/min (calculated according to Cockroft and Gault)

Exclusion Criteria:

• Evidence of metastatic disease in the major viscera or peritoneal seeding or ascites
• Gastric or duodenal obstruction
• Previous peripheral neuropathy
• Previous irradiation to the planned field; previous chemotherapy for pancreatic cancer
• Malignancy (within the past two years) except non-melanomatous skin cancer or carcinoma in situ of the cervix, uterus, or bladder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gem-based doublets with LDR & sequential SBRT; Four Gem-based doublets cycles will be administered concurrent with LDR. If no progression, three fractions of SBRT will be administered.	Radiation: LDR; LDR will be delivered during each cycle of Gem-based doublets; Other Names: Low dose radiotherapy; Drug: Gem-based doublets; 4 cycles of Gem-based doublets; Radiation: SBRT; SBRT will be administered after the fourth Gem-based doblet cycle, if no progression; three fractions will be administered; Other Names: Steretactic body radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	defined as the time from the initiation of therapy to the time of first event (local, regional or distant progression or death due to any cause). Patients without any such event at the time of data analysis will be censored at the last date they were known to be event-free. Patients with no tumor assessments after baseline will be censored at day 1	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity(scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events (v4.0))	Acute gastrointestinal toxicity is defined as adverse events occurring <3 months after SBRT; long-term toxicity was defined as those occurring after 3 months. Toxicity is scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events (v4.0)	every 3 months, up to 1 year
Overall survival	defined as the time from the date of initiation of therapy to date of death due to any cause. Patients who is alive on the date of last follow-up were censored on that date	1 year

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero-Universitaria di Modena
• Investigators: Principal Investigator: Bruno Meduri, MD, Azienda Ospedaliero-Universitaria Policlinico di Modena

Publications and helpful links

General Publications

• Mantini G, Valentini V, Meduri B, Margaritora S, Balducci M, Micciche F, Nardone L, De Rose F, Cesario A, Larici AR, Maggi F, Calcagni ML, Granone P. Low-dose radiotherapy as a chemo-potentiator of a chemotherapy regimen with pemetrexed for recurrent non-small-cell lung cancer: a prospective phase II study. Radiother Oncol. 2012 Nov;105(2):161-6. doi: 10.1016/j.radonc.2012.09.006. Epub 2012 Oct 12.
• Regine WF, Hanna N, Garofalo MC, Doyle A, Arnold S, Kataria R, Sims J, Tan M, Mohiuddin M. Low-dose radiotherapy as a chemopotentiator of gemcitabine in tumors of the pancreas or small bowel: a phase I study exploring a new treatment paradigm. Int J Radiat Oncol Biol Phys. 2007 May 1;68(1):172-7. doi: 10.1016/j.ijrobp.2006.11.045. Epub 2007 Feb 2.
• Mahadevan A, Jain S, Goldstein M, Miksad R, Pleskow D, Sawhney M, Brennan D, Callery M, Vollmer C. Stereotactic body radiotherapy and gemcitabine for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2010 Nov 1;78(3):735-42. doi: 10.1016/j.ijrobp.2009.08.046. Epub 2010 Feb 18.
• Valentini V, Massaccesi M, Balducci M, Mantini G, Micciche F, Mattiucci GC, Dinapoli N, Meduri B, D'Agostino GR, Salvi G, Nardone L. Low-dose hyperradiosensitivity: is there a place for future investigation in clinical settings? Int J Radiat Oncol Biol Phys. 2010 Feb 1;76(2):535-9. doi: 10.1016/j.ijrobp.2009.02.075. Epub 2009 Jun 18.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Anticipated): November 1, 2023
• Study Completion (Anticipated): November 1, 2024

Study Registration Dates

• First Submitted: April 7, 2015
• First Submitted That Met QC Criteria: April 14, 2015
• First Posted (Estimate): April 15, 2015

Study Record Updates

• Last Update Posted (Estimate): December 12, 2022
• Last Update Submitted That Met QC Criteria: December 8, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Locally advanced pancreatic cancer; Stereotactic Body Radiotherapy; Chemopotentiator; Low dose radiotherapy; Hyper-Radiosensitivity
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: BMed1