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

Pancreatic Cancer Clinical Trial

— ORCHESTRATE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02416609
• Other study ID #: BMed1
• Status: Recruiting
• Phase: N/A
• Start date: January 2014
• Est. completion date: November 2024

Study information

• Verified date: December 2022
• Source: Azienda Ospedaliero-Universitaria di Modena
• Contact: Bruno Meduri, MD
• Phone: +393388878319
• Email: brunomeduri[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: November 2024
• Est. primary completion date: November 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Radiation:
• LDR
LDR will be delivered during each cycle of Gem-based doublets

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

Locations

Country	Name	City	State
Italy	Azienda Ospedaliero-Universitaria Policlinico di Modena	Modena	MO

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliero-Universitaria di Modena

Country where clinical trial is conducted

Italy, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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