Rectal Cancer Stage, Oesophageal Cancer
Conditions
Keywords
Rectal Cancer, Oesophageal Cancer, Chemoradiotherapy, Short-course preoperative radiotherapy, PD-L1 PET, 89Zr-atezolizumab
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.
Interventions
RADIATIONCRT
50 Gy in 2 Gy fractions over 25 working days + capecitabine 1650 mg/m2/d PO
RADIATIONSCPRT
25 Gy in 5 Gy fractions over 5 working days
RADIATIONCROSS 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_TESTPD-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.
Sponsors
Johannes Laengle, MD, PhD
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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). |
Countries
Austria
Contacts
Primary ContactJohannes Laengle, MD, PhD
Backup ContactMichael Bergmann, MD
Outcome results
None listed