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

• Sponsor: Johannes Laengle, MD, PhD (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT04564482
• Collaborator: Christian Doppler Laboratory Applied Metabolomics (Other)
• Enrollment: 20
• Location: 1
• Arms: 3
• Anticipated Duration (Months): 20
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Rectal Cancer Stage; Oesophageal Cancer	Radiation: CRT; Radiation: SCPRT; Radiation: CROSS Protocol; Diagnostic Test: PD-L1 PET	N/A

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 20 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• 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
• Anticipated Study Start Date: Oct 1, 2022
• Anticipated Primary Completion Date: Dec 1, 2023
• Anticipated Study Completion Date: Jun 1, 2024

Arms and Interventions

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)	Radiation: SCPRT; 25 Gy in 5 Gy fractions over 5 working days; 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: Neoadjuvant Chemoradiotherapy (CROSS protocol)	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; 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.

Outcome Measures

Primary Outcome Measures

1. Intratumoral changes of PD-L1 expression during neoadjuvant CRT/SCPRT [3 weeks]

   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).

Secondary Outcome Measures

1. Radiographic therapy response [12 weeks]

   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.

2. Pathological therapy response [12 weeks]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical University of Vienna	Vienna		Austria	1090

Sponsors and Collaborators

• Johannes Laengle, MD, PhD
• 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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Johannes Laengle, MD, PhD, Sub-Investigator, Medical University of Vienna
• ClinicalTrials.gov Identifier: NCT04564482
• Other Study ID Numbers: PETNEC; 2020-003142-37
• First Posted: Sep 25, 2020
• Last Update Posted: Aug 23, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Johannes Laengle, MD, PhD, Sub-Investigator, Medical University of Vienna: Rectal Cancer; Oesophageal Cancer; Chemoradiotherapy; Short-course preoperative radiotherapy; PD-L1 PET; 89Zr-atezolizumab
• Additional relevant MeSH terms: Rectal Neoplasms

Study Results

No Results Posted as of Aug 23, 2022