Cancer metastases
Conditions
Interventions
In part A of this imaging trial, a dose finding study will be performed to
establish safety, to assess the appropriate protein dose for PET-scanning
(consisting of a fixed dose of ZED88082A and if r
one at baseline before ICI treatment,
and one during treatment with ICIs at early cycle 2, to minimize morphological
changes in tumors responding to the therapy (with flexibility to adjust the
timi
Sponsors
Universitair Medisch Centrum Groningen
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Subjects with histologically confirmed locally advanced or metastatic cancer for the following tumor types * Cancer types other than melanoma; subjects meeting the eligibility criteria as formulated in the MPDL3280A treatment study protocol (MPDL3280A-treatment-IST-UMCG) are eligible for part A or part B1. * Melanoma; subjects eligible to receive standard of care anti-PD1 therapy plus or minus ipilimumab, are eligible for part B2. 2. Tumor lesion(s) of which a histological biopsy can safely be obtained according to standard clinical care procedures. 3. Measurable disease, as defined by standard RECIST v1.1. Previously irradiated lesions should not be counted as target lesions. 4. Signed informed consent. 5. Age >=18 at the time of signing informed consent. 6. Life expectancy >=12 weeks. 7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 8. Ability to comply with the protocol. 9. For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception (i.e., one that results in a low failure rate [
Exclusion criteria
Exclusion criteria: 1. Potential subjects with cancer other than melanoma will be excluded from participation in this study if they meet exclusion criteria formulated in the MPDL3280A treatment study protocol (MPDL3280A-treatment-IST-UMCG). 2. Signs or symptoms of infection within 2 weeks prior to ZED88082A/CED88004S injection. 3. Prior immune checkpoint inhibitor treatment, including but not limited to anti-PD1 and anti-PD-L1 therapeutic antibodies. 4. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins 5. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of ZED88082A/CED88004S, or that may affect the interpretation of the results or render the patient at high risk from complications. 6. Pregnant or lactating women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Assessment of safety of ZED88082A/CED88004S. Appropriate ZED88082A/CED88004S dosing and appropriate PET imaging time-points. Description of ZED88082A/CED88004S PK by measuring standardized uptake value (SUV) on the ZED88082A/CED88004S-PET scans 0, 2, 4 and/or 7 days after ZED88082A/CED88004S injection before and during immune checkpoint inhibitor treatment. Assessment of immunogenicity by ADA formation. | — |
Secondary
| Measure | Time frame |
|---|---|
| i. Heterogeneity of ZED88082A tumor uptake, evaluated by measuring standardized uptake value (SUV) on the ZED88082A/CED88004S-PET scans 0, 2, 4 and/or 7 days after ZED88082A/CED88004S injection. ii. Safety assessment of side effects as defined according to NCI CTCAE v4.03 considered possibly related to ICI will be correlated to ZED88082A normal organ uptake, evaluated by measuring standardized uptake value (SUV) on the ZED88082A/CED88004S-PET scans performed at baseline and during ICI treatment 0, 2, 4 and/or 7 days after ZED88082A/CED88004S injection. For patients in part A and B1, data on AEs possibly related to ICI will be recorded within the MPDL3280A treatment trial. For melanoma patients in part B2, AEs possibly related to ICI will be separately recorded in the electronical case record form of this imaging trial. Data will be derived from the electronical medical dossier in a prospectively observational way, assessed by investigators or treating physicians* initiative and graded according to CTCAEv4.03. iii. Immune cell CD8 expression and tumor and immune cell PD-L1 expression analyses, as well as evaluation of other markers of lymphocytic infiltration in a tissue biopsy will be correlated to ZED88082A tumor uptake, evaluated by measuring standardized uptake value (SUV) on the ZED88082A/CED88004S-PET scan 0, 2, 4 and/or 7 days after ZED88082A/CED88004S injection. iv. ZED88082A normal organ uptake, evaluated by measuring standardized uptake value (SUV) on the ZED88082A/CED88004S-PET scans 0, 2, 4 and/or 7 days after ZED88082A/CED88004S injection will be correlated to ZED88082A/CED88004S blood kinetics. Aliquots of whole blood and serum samples will be measured for 89Zr-activity in an isotope well counter and corrected for decay to assess ZED88082A concentrations. Whole blood and serum activity will be expressed as standardized uptake value (SUV). Serum samples will also be collected regularly during the study to measure concentrations | — |
Countries
Netherlands
Outcome results
None listed