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

Oesophageal Cancer Clinical Trial

— PETNEC  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04564482
• Other study ID #: PETNEC
• Secondary ID: 2020-003142-37
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2022
• Est. completion date: June 1, 2026

Study information

• Verified date: March 2024
• Source: Medical University of Vienna
• Contact: Johannes Laengle, MD, PhD
• Phone: +43140400 69260
• Email: johannes.laengle[@]meduniwien.ac.at
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: June 1, 2026
• Est. primary completion date: December 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Oesophageal Cancer
• Rectal Cancer Stage
• Rectal Neoplasms

Intervention

Radiation:
• CRT
50 Gy in 2 Gy fractions over 25 working days + capecitabine 1650 mg/m2/d PO
• SCPRT
25 Gy in 5 Gy fractions over 5 working days
• 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

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.

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Johannes Laengle, MD, PhD

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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