PD-L1 PET Imaging During Neoadjuvant (Chemo)Radiotherapy in Esophageal and Rectal Cancer (PETNEC)

Programmed Death-ligand 1 Positron Emission Tomography Imaging During Neoadjuvant (Chemo)radiothErapy in Esophageal and Rectal Cancer (PETNEC): a Prospective Non-randomized Open-label Single-center Pilot Study

The overall aim of this pilot study is to prospectively monitor programmed death-ligand 1 (PD-L1) expression dynamics in vivo, during neoadjuvant chemoradiotherapy (CRT) or short-course preoperative radiotherapy (SCPRT) in rectal and esophageal cancer by a positron emission tomography (PET) imaging approach.

Study Overview

• Status: Recruiting
• Conditions: Oesophageal Cancer; Rectal Cancer Stage
• Intervention / Treatment: Radiation: CRT; Diagnostic test: PD-L1 PET; Radiation: SCPRT; Radiation: CROSS Protocol

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Johannes Laengle, MD, PhD; Phone Number: +43140400 69260; Email: johannes.laengle@meduniwien.ac.at
• Study Contact Backup: Name: Michael Bergmann, MD; Phone Number: +43140400 69260; Email: michael.bergmann@meduniwien.ac.at

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna
    • Principal Investigator: Alexander Haug, MD
    • Sub-Investigator: Michael Bergmann, MD
    • Sub-Investigator: Dietmar Tamandl, MD
    • Sub-Investigator: Rainer Schmid, MD
    • Contact: Johannes Laengle, MD, PhD; Phone Number: +43 1 40400 69260; Email: johannes.laengle@meduniwien.ac.at
    • Sub-Investigator: Johannes Laengle, MD, PhD
    • Contact: Michale Bergmann, MD; Phone Number: +43 1 40400 69260; Email: michael.bergmann@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years of age and older
• All sexes
• Histologically confirmed carcinoma of the rectum or oesophagus (squamous cell carcinoma and adenocarcinoma, including oesophago-gastric junction cancers)
• Medical need for a neoadjuvant CRT/SCPRT
• Suitable to withstand the course of neoadjuvant CRT/SCPRT
• Written informed consent form (ICF) for participation in the study

Exclusion Criteria:

• Metastatic disease, which is considered incurable by local therapies (expect for oligometastatic disease with a curative intend)
• Previous surgery of the tumor other than biopsy
• Pregnancy, breastfeeding or expectancy to conceive
• Prior therapy with anti-CTLA-4, anti-PD-1, anti-PD-L1, anti-PD-L2 or any other agent directed against co-inhibitory T cell receptors or has previously participated in clinical studies with immunotherapy
• Disagreement of participants with reproductive potential to use contraception throughout the study period and for up to 180 days after the last dose of study therapy
• Hepatitis B or C
• Human immunodeficiency virus (HIV)
• Immunodeficiency
• Allogeneic tissue or solid organ transplantation
• Autoimmune disease that has required systemic therapy in the past 2 years with modifying agents, steroids or immunosuppressive drugs
• Active non-infectious pneumonitis
• Active infection requiring systemic therapy
• Systemic steroids or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
• Diagnosed and/or treated additional malignancy within 5 years of randomization, with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin and/or curatively-resected in situ cervical and/or breast cancers
• Treatment with botanical preparations (i.e. herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to randomization/treatment
• Participants with serious or uncontrolled medical disorders
• Uncontrolled or significant cardiovascular disease (myocardial infarction, uncontrolled angina, any history of clinically significant arrhythmias, QTc prolongation in males > 450 ms and > 470 ms in females, participants with history of myocarditis)
• Allergies and adverse drug reaction (history of allergy or hypersensitivity to study drug components, contraindications to any of the study drugs of the chemotherapy regimen)
• Other exclusion criteria: Prisoners or participants who are involuntarily incarcerated, participants who are compulsorily detained for treatment of either a psychiatric or physical (i.e. infectious disease) illness

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Neoadjuvant Chemoradiotherapy (CRT)	Radiation: CRT; 50 Gy in 2 Gy fractions over 25 working days + capecitabine 1650 mg/m2/d PO; Diagnostic test: PD-L1 PET; 10 mg atezolizumab IV followed by 37 MBq 89Zr-atezolizumab IV. PET imaging will be done before neoadjuvant CRT/SCPRT (day 0) and between day 10-14 during CRT/SCPRT.
Other: Short-course preoperative radiotherapy (SCPRT)	Diagnostic test: PD-L1 PET; 10 mg atezolizumab IV followed by 37 MBq 89Zr-atezolizumab IV. PET imaging will be done before neoadjuvant CRT/SCPRT (day 0) and between day 10-14 during CRT/SCPRT.; Radiation: SCPRT; 25 Gy in 5 Gy fractions over 5 working days
Other: Neoadjuvant Chemoradiotherapy (CROSS protocol)	Diagnostic test: PD-L1 PET; 10 mg atezolizumab IV followed by 37 MBq 89Zr-atezolizumab IV. PET imaging will be done before neoadjuvant CRT/SCPRT (day 0) and between day 10-14 during CRT/SCPRT.; Radiation: CROSS Protocol; 41.4 Gy in 1.8 Gy fractions over 23 working days + carboplatin AUC of 2 mg/ml/min + paclitaxel 50 mg/m2 IV Q1W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intratumoral changes of PD-L1 expression during neoadjuvant CRT/SCPRT	Intratumoral PD-L1 expression dynamics induced by neoadjuvant CRT/SCPRT will be assessed by 89Zr-atezolizumab PET imaging (day 0 and between day 10-14).	3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic therapy response	Radiographic therapy response will be determined by magnetic resonance imaging-assessed tumor regression grade (mrTRG) for rectal cancer and PET response criteria in solid tumors (PERCIST) for esophageal cancer.	12 weeks
Pathological therapy response	Pathological therapy response will be determined according to the latest American Joint Committee on Cancer/International Union Against Cancer-Tumor Node Metastasis (AJCC/UICC-TNM) staging and tumor regression grade (TRG).	12 weeks

Collaborators and Investigators

• Sponsor: Johannes Laengle, MD, PhD
• Collaborators: Christian Doppler Laboratory Applied Metabolomics
• Investigators: Principal Investigator: Alexander Haug, MD, Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2022
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: September 15, 2020
• First Submitted That Met QC Criteria: September 21, 2020
• First Posted (Actual): September 25, 2020

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Rectal Cancer; Chemoradiotherapy; Oesophageal Cancer; Short-course preoperative radiotherapy; PD-L1 PET; 89Zr-atezolizumab
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: PETNEC; 2020-003142-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No