lungcancer non-small cell lungcancer
Conditions
Interventions
1: Dose optimization for PD-L1 PET/CT
In three groups of five patients with NSCLC, the first 5 receive an antibody
dose of 2 mg, the following two groups will receive 10 and 50 mg 89Zr-avelumab.
Wh
anti-PD-L1
immunotherapy
molecular imaging
NSCLC
Sponsors
Radboud Universitair Medisch Centrum
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Male or female subjects aged * 18 years and >50 years in patients with resectable stage Ia (*T1b tumor) - IIIa NSCLC 2. Histological or cytologic proven stage IIIb/IV NSCLC or resectable stage Ia (*T1b tumor) - IIIa NSCLC 3. ECOG performance score (0-1)Karnofsky performance score * 70 4. At least one lesion with a tumor size * 1 cm 5. Hematologic function: absolute neutrophil count (ANC) * 1.5 × 109/L, platelet count * 100 × 109/L, and hemoglobin * 9 g/dL (may have been transfused) 6. Hepatic function: total bilirubin level * 1.5 × the upper limit of normal (ULN) range and AST and ALT levels * 2.5 × ULN for all subjects or AST and ALT levels * 5 x ULN (for subjects with documented metastatic disease to the liver). 7. Estimated creatinine clearance * 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method) 8. Highly effective contraception for both male and female subjects throughout the study and for at least 60 days after avelumab treatment administration if the risk of conception exists. (Note: The effects of the trial drug on the developing human foetus are unknown; thus, women of childbearing potential and men able to father a child must agree to use 2 highly effective contraception, defined as methods with a failure rate of less than 1 % per year. Highly effective contraception is required at least 28 days prior, throughout and for at least 60 days after avelumab treatment.) 9. Fit for surgery (for patients with resectable stage Ia-IIIa disease), as assessed by treating thoracic surgeon / anesthesiologists based on sufficient cardiopulmonary status and absence of major contra-indications for surgery according to local guidelines
Exclusion criteria
Exclusion criteria: 1. All subjects with brain metastases, except those meeting the following criteria: * Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrollment * No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable) * Subjects must be either off steroids or on a stable or decreasing dose of 1 NCI-CTCAE v 4.03; however, alopecia and sensory neuropathy Grade * 2 is acceptable 7. Pregnancy or lactation 8. Known alcohol or drug abuse 9. Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study. 10. Any psychiatric condition that would prohibit the understanding or rendering of informed consent 11. Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines 12. Immunosuppressants: *Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (eg, intra-articular injection); b. Systemic corticosteroids at physiologic doses * 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).* 13. Cardiovascular disease: *Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end points Study 1: Tumor uptake of 89Zr-avelumab Study 2: Validation of PD-L1 imaging | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end points Study 1: 1. Heterogeneity of 89Zr-avelumab uptake within and between tumor lesions 2. Correlation between 89Zr-avelumab tumor uptake and PD-L1 expression Study 2: 1. Correlation between tumor uptake of 89Zr-avelumab in the individual tumor lesions and pathologic response after neo-adjuvant avelumab treatment 2. Correlation between tumor uptake of 89Zr-avelumab in the individual tumor lesions and overall survival after neo-adjuvant avelumab treatment and surgery 3. Correlation between PD-L1 expression on tumor cells before and after neo-adjuvant avelumab treatment 4. Pathological response to neo-adjuvant avelumab treatment in patients with resectable stage Ia (*T1b tumor) -IIIa NSCLC 5. Local increase in CD8+ T-cells and tumor infiltration of CD8+ T-cells together with a cytokine influx after neo-adjuvant treatment 6. Safety of neo-adjuvant avelumab in NSCLC 7. The number of treatment-related delays in surgical resections 8. The number of VATS conversions after neo-adjuvant avelumab 9. Post-operative complications incl. length of hospital stay and 30 and 90 day mortality. | — |
Countries
The Netherlands
Outcome results
None listed