Advanced melanoma MedDRA version: 21.1 Level: PT Classification code 10025671 Term: Malignant melanoma stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10025670 Term: Malignant melanoma stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: ipilimumab-zirconium-89
Product Code: 89Zr-ipilimumab
Pharmaceutical Form: Solution for injection/infusion in pre-filled syringe
INN or Proposed INN: IPILIMUMAB
CAS Number: 477202-00-9
C
Sponsors
VU medical center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Advanced/metastatic melanoma o Scheduled for treatment with combination treatment of nivolumab and ipilimumab. o Age = 18 years. o Histological or cytological documentation of cancer is required. o WHO Performance Status of 0 or 1. o At least 1 measurable lesion. o Signed informed consent must be obtained prior to any study procedures. o Patients must be able to adhere to the study appointments and other protocol requirements. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 24 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 24
Exclusion criteria
Exclusion criteria: o Previous exposure to ipilimumab or nivolumab. o Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start treatment. Both men and women enrolled in this trial must agree to use adequate barrier birth control measures (e.g. cervical cap, condom and diaphragm) during the course of the trial. Oral birth control methods alone will not be considered adequate on this study, because of the potential pharmacokinetic interaction between study drug and oral contraceptives. Concomitant use of oral and barrier contraceptives is advised. Contraception is necessary for at least 6 months after receiving study drug. o Concurrent anticancer chemotherapy, immunotherapy or investigational drug therapy during the study or within 4 weeks after starting the study drug. o Radiotherapy of target lesions during study or within 4 weeks after starting the study drug. Palliative radiotherapy will be allowed. o Major surgery within 28 days of start of study drug. o Substance abuse, medical, psychological or social conditions that may interfere with the subject’s participation in the study or evaluation of the study results. o Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess uptake (visual and quantitative) of 89Zr-ipilimumab in tumor lesions and biodistribution before and after start of ipilimumab/nivolumab combination therapy.;Secondary Objective: 1.To determine the correlation between tumor targeting of ipilimumab and response to therapy. 2.To assess uptake (visual and quantitative) of 89Zr-ipilimumab in normal tissues, with special attention to gut, lung, liver and pituitary, before and after start of ipilimumab/nivolumab combination therapy. 3.To determine the correlation between organ (e.g. GI-tract, skin, liver) targeting and toxicity. 4.To determine whether tumor related, pre-treatment CTLA-4 expression in CD4+ T cells in blood is associated with improved survival after ipilimumab treatment. 5.To determine the correlation between pre-treatment CTLA-4 expression in CD4+ T cells in blood and uptake of 89Zr-ipilimumab in tissues. 6.To determine the correlation between inflammatory infiltrate in tumor tissue and uptake of 89Zr-ipilimumab.;Primary end point(s): The detection (visual = uptake above local background, and quantitative = SUV) of 89Zr-ipilimumab in tumor lesions (the short axis diameter of a measurable tumor lesion is =1 cm. The five largest lesions will be used for evaluation; quantification will be done in lesions >2 cm to avoid partial volume effects).;Timepoint(s) of evaluation of this end point: In part 1: one week before first injection of nivolumab/ipilimumab combination treatment, scans will be obtained 72, 96 and 144h after injection. In 5 patients also after second cycle of nivolumab/ipilimumab treatment scans will be obtained 72, 96 and 144h. in part 2 only 1 scan will be obtained at the optimal time point determined in part 1. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Clinical outcome: - Response after starting therapy with ipilimumab at 12 and 24 weeks and every 12 weeks thereafter. For melanoma patients response will be assessed by CT-scan using the mWHO and irRC. - Overall survival. 2. The detection of 89Zr-ipilimumab in normal tissue in week -2 (before first injection if ipilimumab) and in week 4 (after second injection of ipilimumab): - visual: Description of the biodistribution. - quantitative: The % uptake (of total injected) 89Zr-ipilimumab in normal tissue, measured in VOI’s. - comparison between uptake (SUVmean and SUVpeak) of 89Zr-ipilimumab before the first injection of nivolumab/ipilimumab and after the second cycle. 3. Side effects: - Adverse events using Common Terminology Criteria Adverse Events, version 4.0 (CTCAE 4.0). - Correlation between side effects of ipilimumab and uptake of 89Zr-ipilimumab in normal tissue. 4. Other study parameters: -CTLA-4+CD4+ expression of PBMCs at 6 time points (whole blood sample): pre-treatment, at t = 60 minutes and t = 72 hours after first and after second injection of ipilimumab. - Correlation between CTLA-4+CD4+ expression of PBMCs and uptake of 89Zr-ipilimumab in tissues. - Pharmacokinetics of 89Zr-ipilimumab. The concentration of ipilimumab in blood samples will be measured at t = 5, 30, 60, 120 minutes and 72, 96, 144 hours after injection of 89Zr-ipilimumab in the first three patients. - The SUV in tumor lesions will be compared to the SUV in blood. Specific uptake of ipilimumab in tumor lesions is defined as SUVtumor/SUVblood >1.;Timepoint(s) of evaluation of this end point: See above | — |
Countries
Netherlands
Contacts
Public ContactTrial Office Medical Oncology VUmc
VU medical center
Outcome results
None listed